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enkephalin, d-penicillamine (2,5)-

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Description

Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

DPDPE : A heterodetic cyclic peptide that is a cyclic enkephalin analogue, having D-penicillaminyl residues located at positions 2 and 5, which form the heterocycle via a disulfide bond. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID104787
CHEMBL ID31421
CHEBI ID73356
SCHEMBL ID727022
MeSH IDM0328765

Synonyms (56)

Synonym
(4s,7s,13s)-13-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3,3,14,14-tetramethyl-6,9,12-trioxo-7-(phenylmethyl)-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid
gtpl1608
d-valine, l-tyrosyl-3-mercapto-d-valylglycyl-l-phenylalanyl-3- mercapto-, cyclic (2-5)-disulfide
d-valine, l-tyrosyl-3-mercapto-d-valylglycyl-l-phenylalanyl-3-mercapto-, cyclic (2>5)-disulfide (9ci)
1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid, 13-[[(2s)-2-amino-3-(4-hydroxyphenyl)-1-oxopropyl]amino]-3,3,14,14-tetramethyl-6,9,12-trioxo-7-(phenylmethyl)-, (4s,7s,13s)-
88373-73-3
(d-pen2,d-pen5)-enkephalin
cyclic(d-penicillamine2,5)enkephalin
[d-pen2, d-pen5]enkephalin
[d-pen2,5]enkephalin
1,2-dithia-5,8,11-triazacyclotetradecane, cyclic peptide deriv.
cyclic [d-pen2, d-pen5]enkephalin
tyr-d-pen-gly-phe-d-pen [disulfide bridge: 2-5]
[2-d-penicillamine, 5-d-penicillamine]enkephalin
enkephalin, [tyrosyl-2,6-3h(n)]- (2-d-penicillamine, 5-d-penicillamine)
dpdpe-oh
chembl31421 ,
[3h]dpdpe
dpdpe-cl
bdbm21008
(4s,7s,13s)-13-[(2s)-2-amino-3-(4-hydroxyphenyl)propanamido]-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid
dpdpe
d-valine, l-tyrosyl-3-mercapto-d-valylglycyl-l-phenylalanyl-3-mercapto-, cyclic (2-5)-disulfide
enkephalin, d-penicillamine (2,5)-
dpdpe(sh)2
bis-penicillamine-enkephalin
d-penicillamine (2,5)-enkephalin
dplpe
bis-pen-enkephalin
chebi:73356 ,
(4s,7s,13s)-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-13-(l-tyrosylamino)-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid
(4s,7s,13s)-13-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid
C20164
pen(2),pen(5)-enkephalin
enkephalin, penicillamine(2,5)-
2,5-pen-enkephalin
ly 198572
(d-pen(2),d-pen(5))enkephalin
cyclo-[d-pen(2,5)]-enkephalin
h-tyr-c(d-pen-gly-phe-d-pen)-oh
h-tyr-cyclo-(d-pen-gly-phe-d-pen)-oh
c[d-pen(2,5)]-enkephalin
[d-pen(2)-d-pen(5)]-enkephaline
l-tyrosyl-3-mercapto-d-valylglycyl-l-phenylalanyl-3-mercapto-d-valine, cyclic (2-5)-disulfide
d-penicillamine-(2,5)-enkephalin
SCHEMBL727022
[d-pen2,d-pen5]enkephalin
(d-pen2,pen5)-enkephalin
[d-pen2,5]-enkephalin hydrate, >=95% (hplc)
DB08861
cyclo-[d-pen2,5]-enkephalin
[d-pen2-d-pen5]-enkephaline
(4s,7s,13s)-13-((s)-2-amino-3-(4-hydroxyphenyl)propanamido)-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid
Q27077106
DTXSID201008102
d-valine, l-tyrosyl-3-mercapto-d-valylglycyl-l-phenylalanyl-3-mercapto-, cyclic (2?5)-disulfide

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" This investigation assesses pharmacodynamic and pharmacokinetic characteristics of PEG-conjugated [D-Pen2,D-Pen5]-enkephalin (DPDPE), a met-enkephalin analog, in rodent (in vivo, in situ) and bovine (in vitro) systems."( Pharmacodynamic and pharmacokinetic characterization of poly(ethylene glycol) conjugation to met-enkephalin analog [D-Pen2, D-Pen5]-enkephalin (DPDPE).
Bentley, MD; Davis, TP; Egleton, RD; Guo, L; Huber, JD; Roberts, MJ; Wei, H; Witt, KA; Yamamura, HI, 2001
)
0.31
" Results of pharmacokinetic modeling were consistent with the hypothesis that GF120918 inhibited a [3H]DPDPE basolateral excretion mechanism."( Hepatobiliary disposition of the metabolically stable opioid peptide [D-Pen2, D-Pen5]-enkephalin (DPDPE): pharmacokinetic consequences of the interplay between multiple transport systems.
Brouwer, KL; Hoffmaster, KA; Pollack, GM; Zamek-Gliszczynski, MJ, 2004
)
0.32
" The fentanyl concentrations derived by both methods were compared by linear regression and pharmacokinetic analysis."( Comparison of liquid chromatography-mass spectrometry and radioimmunoassay for measurement of fentanyl and determination of pharmacokinetics in equine plasma.
Mama, KR; Stanley, SD; Thomasy, SM,
)
0.13

Compound-Compound Interactions

ExcerptReferenceRelevance
" The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined."( Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H.
Collins, JG; Harada, Y; Kishikawa, K; Kitahata, LM; Nishioka, K, 1995
)
0.29

Bioavailability

ExcerptReferenceRelevance
" administration, large amounts of [3H]DPDPE were found in the small intestine and flush, but not until 60 min postadministration, suggesting a slower rate of absorption from the site of administration."( Whole body and brain distribution of [3H]cyclic [D-Pen2,D-Pen5] enkephalin after intraperitoneal, intravenous, oral and subcutaneous administration.
Davis, TP; Greene, DL; Hruby, VJ; Porreca, F; Weber, SJ; Yamamura, HI, 1992
)
0.28
" The extent to which these effects can be attributed to changes in drug pharmacokinetics and bioavailability versus sensitivity of the neuronal circuits that mediate the affected behavioral functions, has not been established."( Chronic food restriction in rats augments the central rewarding effect of cocaine and the delta1 opioid agonist, DPDPE, but not the delta2 agonist, deltorphin-II.
Cabeza de Vaca, S; Carr, KD; Kim, GY, 2000
)
0.31
", ip) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule."( Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents.
Bednarski, M; Gunia-Krzyżak, A; Marona, H; Nitek, W; Pękala, E; Powroźnik, B; Słoczyńska, K; Walczak, M; Waszkielewicz, AM; Żesławska, E, 2016
)
0.43
" To develop stable and orally bioavailable analogues of DN-9, eight lactam-bridged cyclic analogues of DN-9 between positions 2 and 5 were designed, synthesized, and biologically evaluated."( Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
Chen, D; Fang, Q; Li, N; Niu, J; Shi, X; Shi, Y; Xiao, J; Xu, B; Xu, K; Zhang, M; Zhang, Q; Zhang, R, 2021
)
0.62

Dosage Studied

ExcerptRelevanceReference
" This observation can be interpreted as indication that within this dosage range there is an absence of morphine-like subjective effects."( Analogs of the delta opioid receptor selective cyclic peptide [2-D-penicillamine,5-D-penicillamine]-enkephalin: 2',6'-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions.
Anthony, E; Beardsley, PM; Chandrakumar, NS; Drury, B; Lopez, OT; Reichman, M; Savage, MA; Stapelfeld, A; Williamson, LN, 1992
)
0.28
" Different potencies in stimulating the low Km GTPase was observed at sub-maximal agonist concentrations, although the shallow dose-response behavior did not allow accurate determination of ED50s."( Assessment of delta-opioid receptor activation by a series of peptides in cultured cells.
Costa, EM; Hoffman, BB; Loew, GH, 1992
)
0.28
" agonist dose-response curves by theophylline (i."( Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice.
DeLander, GE; Mosberg, HI; Porreca, F, 1992
)
0.28
" catheters, dose-response curves were carried out using the hot plate (HP) test for a number of receptor-preferring opioids."( Characteristics of dose-dependent antagonism by beta-funaltrexamine of the antinociceptive effects of intrathecal mu agonists.
Mjanger, E; Yaksh, TL, 1991
)
0.28
"8-fold rightward shift in the dose-response curve."( Lack of antinociceptive cross-tolerance between [D-Pen2, D-Pen5]enkephalin and [D-Ala2]deltorphin II in mice: evidence for delta receptor subtypes.
Mattia, A; Mosberg, HI; Porreca, F; Vanderah, T, 1991
)
0.28
" Upon pretreatment with morphine over greater than or equal to 12 h, a fourfold shift of the PGE1-morphine dose-response curve was observed, whether or not IBMX was added."( Regulation of cyclic AMP by the mu-opioid receptor in human neuroblastoma SH-SY5Y cells.
Duan, DS; Eiger, S; Lameh, J; Sadée, W; Yu, VC, 1990
)
0.28
" On the basis of our dose-response data, we suggest that, in mice, kappa and mu, but not delta, opioid receptors modulate tonic pain perception at both spinal and supraspinal loci."( Tonic pain perception in the mouse: differential modulation by three receptor-selective opioid agonists.
Cowan, A; Murray, CW, 1991
)
0.28
" However, when the dose-response curves for both U50, 488H and DPDPE in the presence of a low-analgesic dose of the other agent were compared with the dose-response curves for the respective agonist administered alone, the curves for the combination regimens were shifted to the left."( Kappa- and delta-opioid agonists synergize to produce potent analgesia.
Levine, JD; Miaskowski, C; Taiwo, YO, 1990
)
0.28
" On day 6, the magnitude of tolerance was assessed by establishing IT dose-response lines for the effect of the chronic drug given as bolus injections (probe)."( Tolerance to delta- but not mu-opioid receptors in the spinal cord attenuates inhibition of the tail-flick response induced by beta-endorphin administered intracerebroventricularly in mice.
Suh, HH; Tseng, LF, 1990
)
0.28
" Proglumide both shifted the dose-response curve for morphine analgesia to the left and prolonged morphine's duration of action."( Proglumide selectively potentiates supraspinal mu 1 opioid analgesia in mice.
Bodnar, RJ; Pasternak, GW; Paul, D, 1990
)
0.28
" The FHR response to DADLE was similar to DAGO in both dose-response and time-action characteristics."( Central opioid modulation of fetal cardiovascular function: role of mu- and delta-receptors.
Cai, LQ; Szeto, HH; Zhu, YS, 1990
)
0.28
" morphine dose-response line was shown to be displaced progressively to the right with decreasing maximal effect (i."( Modulation of the potency and efficacy of mu-mediated antinociception by delta agonists in the mouse.
Mosberg, HI; Porreca, F; Qi, JN, 1990
)
0.28
" Graded dose-response curves (DRC) were constructed from tail-flick latencies converted to % maximal possible effect (%MPE), and the ED50 calculated."( Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: isobolographic analysis.
Green, J; Harris, S; Lloyd, P; Lozito, R; Messineo, E; Ossipov, MH, 1990
)
0.28
" Both the morphine and normorphine dose-response lines were displaced to the left in the presence of DPDPE."( Modulation of mu-mediated antinociception by delta agonists in the mouse: selective potentiation of morphine and normorphine by [D-Pen2,D-Pen5]enkephalin.
Haaseth, RC; Heyman, JS; Mosberg, HI; Porreca, F; Vaught, JL, 1989
)
0.28
" Naloxonazine shifted the supraspinal DAGO dose-response curve 4-fold to the right without changing the curve for spinal DAGO."( Different mu receptor subtypes mediate spinal and supraspinal analgesia in mice.
Bodnar, RJ; Gistrak, MA; Pasternak, GW; Paul, D, 1989
)
0.28
" The slopes of the dose-response lines were parallel, but the delta compound was about 250 times less potent than DAMGO."( Sympathoadrenal, cardiovascular and blood gas responses to highly selective mu and delta opioid peptides.
Kiritsy-Roy, JA; Marson, L; Van Loon, GR, 1989
)
0.28
", DPDPE displaced the morphine dose-response line to the left and also potentiated the effects of normorphine and etorphine."( Differential modulation by [D-Pen2, D-Pen5]enkephalin and dynorphin A-(1-17) of the inhibitory bladder motility effects of selected mu agonists in vivo.
Nunan, L; Porreca, F; Sheldon, RJ, 1989
)
0.28
" As is seen for [Leu]enkephalin when tested in a one-way active avoidance task, the dose-response function for the impairment produced by DPen2-[DPen5]enkephalin in the automated shelf-jump task is U-shaped."( DPen2-[DPen5]enkephalin, a delta opioid receptor-selective analog of [Leu]enkephalin, impairs avoidance learning in an automated shelf-jump task in rats.
Gehrig, CA; Martinez, JL; Weinberger, SB, 1989
)
0.28
" Antinociceptive dose-response curves were constructed for mu ([D-Ala2,NMePhe4,Gly-ol]enkephalin, DAGO; morphine) and delta ([D-Pen2,D-Pen5]enkephalin, DPDPE)-agonists in the absence, and in the presence of the mu non-surmountable antagonist, beta-funaltrexamine (beta-FNA) or the delta-antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, where Aib is alpha-amino-isobutyric acid)."( Opioid delta-receptor involvement in supraspinal and spinal antinociception in mice.
Heyman, JS; Mosberg, HI; Mulvaney, SA; Porreca, F, 1987
)
0.27
" The dose-response curves of the preferential mu- ligands morphine and [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) were shifted by naloxone at low doses but not by ICI 174,864."( The role of mu- and delta- opioid receptors on the intestinal propulsion in rats.
La Regina, A; Petrillo, P; Sbacchi, M; Tavani, A, 1986
)
0.27
"5 microgram/hr) for 5 days caused 61- and 6-fold shifts to the right of the dose-response curves for PL-17 and DPDPE, respectively."( Interaction between highly selective mu and delta opioids in vivo at the rat spinal cord.
Chang, KJ; Leslie, JB; Russell, RD; Su, YF; Watkins, WD, 1986
)
0.27
" In an effort to examine the receptor subtypes responsible for opioid analgesia in specific brain regions, we examined dose-response relationships and naloxonazine sensitivity of morphine and two enkephalin derivatives in the above 4 brain regions."( Role of mu 1-opiate receptors in supraspinal opiate analgesia: a microinjection study.
Bodnar, RJ; Lee, SJ; Pasternak, GW; Williams, CL, 1988
)
0.27
" Incubation of increasing concentrations of ICI 174,864 (10,30,100 and 300 nM) produced a dose-related and parallel rightward displacement of the DPDPE dose-response curve in the MVD."( Studies in vitro with ICI 174,864, [D-Pen2, D-Pen5]-enkephalin (DPDPE) and [D-Ala2, NMePhe4, Gly-ol]-enkephalin (DAGO).
Burks, TF; Hirning, LD; Hruby, VJ; Hurst, R; Mosberg, HI; Porreca, F, 1985
)
0.27
" pairs of time-response curves, pairs of dose-response lines were constructed at various times; these lines showed decreasing displacement with time, indicative of the disappearance of naloxone."( Estimation of the affinity of naloxone at supraspinal and spinal opioid receptors in vivo: studies with receptor selective agonists.
Heyman, JS; Koslo, RJ; Mosberg, HI; Porreca, F; Tallarida, RJ, 1986
)
0.27
" The slope of the analgesic dose-response curve for the highly specific delta agonist, cyclic [D-Penicillamine2, D-Penicillamine5]enkephalin (DPDPE), was significantly different (flatter) from those of mu agonists or DADLE."( Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors.
Chang, KJ; Leslie, JB; Russell, RD; Su, YF; Watkins, WD, 1987
)
0.27
", the morphine dose-response curve shifted to the left and the ED50 value of morphine decreased."( Effects of a highly selective nonpeptide delta opioid receptor agonist, TAN-67, on morphine-induced antinociception in mice.
Endoh, T; Misawa, M; Mori, T; Nagase, H; Suzuki, T; Tsuji, M, 1995
)
0.29
" The pellets were removed and 24 h later, mice were sacrificed and binding studies were conducted, or mice were tested in analgesia (tail-flick) dose-response studies."( Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: relationship to receptor selectivity.
Chan, K; Davis, T; Duttaroy, A; Shah, S; Yoburn, BC,
)
0.13
" Bicuculline (GABAA receptor antagonist) and picrotoxin (chloride ion channel blocker) given intrathecally produced rightward shifts in the dose-response curves of DPDPE and heroin given intracerebroventricularly."( Spinal GABA receptors mediate brain delta opioid analgesia in Swiss Webster mice.
Fujimoto, JM; Rady, JJ, 1995
)
0.29
" Pretreatment also shifted to the right the dose-response function for DALA intra-accumbens."( Mesoaccumbens dopamine-opiate interactions in the control over behaviour by a conditioned reinforcer.
Everitt, BJ; Phillips, GD; Robbins, TW, 1994
)
0.29
" In contrast, caudal ventral pallidal DPDPE microinjections showed a dose-response effect with reward increases of 19, 22 and 31% (-0."( Comparison of delta opiate receptor agonist induced reward and motor effects between the ventral pallidum and dorsal striatum.
Johnson, PI; Stellar, JR, 1994
)
0.29
" Second, intrathecal administration of 2-hydroxysaclofen, a GABAB antagonist (which inhibited antinociception induced by a GABAB agonist, baclofen, given IT), produced a shift of the dose-response curve for ICV DPDPE to the right."( [D-Pen2-D-Pen5]enkephalin, a delta opioid agonist, given intracerebroventricularly in the mouse produces antinociception through medication of spinal GABA receptors.
Fujimoto, JM; Holmes, BB, 1994
)
0.29
" This EEG activation was greatly attenuated at DPDPE doses greater than 154 nmol/h, resulting in a U-shaped dose-response curve."( Effects of the delta-opioid agonist, [D-Pen2,D-Pen5]-enkephalin, on fetal lamb EEG.
Cheng, PY; Soong, Y; Szeto, HH; Wu, DL, 1994
)
0.29
" Naloxone shifted to the right the dose-response curves for each opioid peptide significantly enhancing the ED50 values."( Modulation of non-adrenergic non-cholinergic inhibitory transmission in rat duodenum: role of opiates and 5-hydroxytryptamine.
Adamo, EB; Di Giovanni, G; Marini, R; Mulè, F; Postorino, A; Serio, R, 1993
)
0.29
" Dose-response curves were generated for both delta 9-THC (i."( Interactions between delta 9-tetrahydrocannabinol and kappa opioids in mice.
Martin, BR; Smith, PB; Welch, SP, 1994
)
0.29
"03 microgram of DAMGO resulting in a steeper dose-response relationship."( Evidence for delta opioid receptor subtypes in rat spinal cord: studies with intrathecal naltriben, cyclic[D-Pen2, D-Pen5] enkephalin and [D-Ala2, Glu4]deltorphin.
Hammond, DL; Stewart, PE, 1993
)
0.29
" This close temporal and dose-response relationship strongly suggests that delta-opioid receptor-mediated increases in intracellular [Ca2+] results from inositol 1,4,5-trisphosphate-induced Ca2+ release from intracellular stores, in undifferentiated NG108-15 cells."( delta-Opioids stimulate inositol 1,4,5-trisphosphate formation, and so mobilize Ca2+ from intracellular stores, in undifferentiated NG108-15 cells.
Lambert, DG; Smart, D, 1996
)
0.29
" However, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta 1-opioid receptor agonist, and [D-Ala2,Cys4]deltorphin, a delta 2-opioid receptor agonist, at doses which exhibit no intrinsic effects (10(-8) and 10(-7) M), shifted the dose-response curve for mu-opioid receptor-evoked adenosine release to the left in a dose-dependent manner."( Synergy between mu/delta-opioid receptors mediates adenosine release from spinal cord synaptosomes.
Cahill, CM; Sawynok, J; White, TD, 1996
)
0.29
" Buprenorphine, when injected systemically, revealed a potent analgesic effect by tailflick assay, with a biphasic dose-response curve, which was reversed by naloxone."( Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with kappa 3 analgesia.
Peter, Y; Pick, CG; Schreiber, S; Weizman, R, 1997
)
0.3
" Pairing Delt II (5 microg) with low (100-200 mg/kg) 2DG doses significantly enhanced intake, producing a leftward (3-fold) shift in 2DG's hyperphagic dose-response curve."( Delta and kappa opioid receptor subtypes and ingestion: antagonist and glucoprivic effects.
Bodnar, RJ; Ruegg, H; Yu, WZ, 1997
)
0.3
" Naloxone (1 microM) or norbinaltorphimine (10 nM) shifted the dose-response curve of (-)-U50,488H to the right by 100-fold."( Activation of the cloned human kappa opioid receptor by agonists enhances [35S]GTPgammaS binding to membranes: determination of potencies and efficacies of ligands.
Chen, C; Li, JG; Liu-Chen, LY; Luo, LY; Zhu, J, 1997
)
0.3
" Administration of morphine, DPDPE, or U50,488H three times daily for 3 days according to an escalating dosing schedule resulted in analgesic tolerance as indicated by an increase in analgesic ED50 values using the tail-flick test in mice."( The competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist LY293558 attenuates and reverses analgesic tolerance to morphine but not to delta or kappa opioids.
Inturrisi, CE; Kao, B; Kest, B; McLemore, G, 1997
)
0.3
" Similarly, the progressive and complete loss of analgesia in CD-1 mice seen with repeated dosing of the delta ligand [D-Pen2, D-Pen5]enkephalin is not observed in 129/SvEv mice."( Lack of morphine and enkephalin tolerance in 129/SvEv mice: evidence for a NMDA receptor defect.
Jain, S; Kolesnikov, Y; Pasternak, GW; Wilson, R, 1998
)
0.3
" After NMDA treatment, the DPDPE dose-response curve shifted to the right (EC50 value increased approximately 7-fold, from 6 to 40 nM), and the maximal response induced by DPDPE was reduced by approximately 60%."( N-Methyl-D-aspartate attenuates opioid receptor-mediated G protein activation and this process involves protein kinase C.
Fan, GH; Jing, Q; Lou, LG; Ma, L; Pei, G; Wu, YL; Zhang, Z; Zhao, J, 1998
)
0.3
" Whereas the dose-response curves to Ins(1,4,5)P3 formation and cyclic AMP inhibition remained largely unaffected by C-terminal truncation, there were large differences in the pEC/IC50 values, with cyclic AMP inhibition being the more potent, perhaps indicating G(i alpha) coupling to adenylyl cyclase and G(i beta/gamma) coupling to PLC."( Effects of C-terminal truncation of the recombinant delta-opioid receptor on phospholipase C and adenylyl cyclase coupling.
Devi, LA; Hirst, RA; Lambert, DG; Smart, D, 1998
)
0.3
" A subsequent dose-response experiment examined the impact of P-gp on DPDPE antinociception."( Altered disposition and antinociception of [D-penicillamine(2,5)] enkephalin in mdr1a-gene-deficient mice.
Chen, C; Pollack, GM, 1998
)
0.3
" Morphine analgesia was inhibited by dynorphin as shown by a rightward shift of the morphine dose-response curve."( Antianalgesic action of dynorphin A mediated by spinal cholecystokinin.
Fujimoto, JM; Holmes, BB; Rady, JJ, 1999
)
0.3
" The dose-response curves for C-fibre evoked response and post-discharge of the neurones were not different in rats aged P14 and P21."( Electrophysiological studies on the postnatal development of the spinal antinociceptive effects of the delta opioid receptor agonist DPDPE in the rat.
Dickenson, AH; Rahman, W, 1999
)
0.3
" with a placebo or 15 mg naltrexone pellet for 8 days, the pellets removed and 24 hr later opioid receptor density (mu, delta) and receptor mRNA level (mu) determined in whole brain; or morphine dose-response studies conducted."( Opioid receptor upregulation in mu-opioid receptor deficient CXBK and outbred Swiss Webster mice.
Carroll, J; Chen, B; Duttaroy, A; Sehba, F; Shah, S; Shen, J; Yoburn, BC, 1999
)
0.3
" Diazoxide (2 microg/mouse) shifted morphine's dose-response curve 47-fold, while levcromakalim (0."( ATP-gated K(+) channel openers enhance opioid antinociception: indirect evidence for the release of endogenous opioid peptides.
Lohmann, AB; Welch, SP, 1999
)
0.3
" Both shifted the dose-response curve of morphine to the right and these actions were eliminated by intrathecal PGD(2."( Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice.
Campbell, WB; Fujimoto, JM; Rady, JJ, 2001
)
0.31
" The Ca(2+) response occurred in all-or-none fashion and the half-maximal dosage of U50488H (812."( Cyclic AMP regulates the calcium transients released from IP(3)-sensitive stores by activation of rat kappa-opioid receptors expressed in CHO cells.
Allen, CN; Grandy, DK; Ikeda, M; Nelson, CS; Shinagawa, H; Shinoe, T; Sugiyama, T; Yoshioka, T, 2001
)
0.31
" NTB (30 nM) shifted the dose-response curve of DAMGO to the right and attenuated the maximal effect."( Pharmacological effects of naltriben as a ligand for opioid mu and kappa receptors in rat cerebral cortex.
Cho, KP; Kim, KW; Shin, BS; Son, Y, 2001
)
0.31
" Furthermore, LY294002 at 33 nmol significantly shifted the dose-response curves for DAMGO-, DPDPE- and [D-Ala(2)]deltorphin II-induced antinociception to the right."( Implications of phosphoinositide 3-kinase in the mu- and delta-opioid receptor-mediated supraspinal antinociception in the mouse.
Narita, M; Nemoto, M; Ohnishi, O; Suzuki, T; Yajima, Y, 2002
)
0.31
" A separate group of animals was used to investigate the dose-response effect on this motor dysfunction."( Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats.
Davison, KJ; Fuchigami, T; Kakinohana, M; Marsala, M; Nakamura, S; Sugahara, K, 2006
)
0.33
" None of the drugs affected the residual volume, micturition threshold pressure or bladder contraction pressure at any dosage examined."( Effects of opioid subtypes on detrusor overactivity in rats with cerebral infarction.
Ishiura, Y; Komatsu, K; Nagasaka, Y; Nakamura, Y; Namiki, M; Yokoyama, O, 2007
)
0.34
" However, following priming (15 min) with bradykinin or arachidonic acid, DPDPE produced a significant reduction in allodynia that was antagonist reversible, peripherally restricted, and exhibited a typical dose-response relationship."( Peripheral delta opioid receptors require priming for functional competence in vivo.
Berg, KA; Clarke, WP; Hargreaves, KM; Patwardhan, AM; Rowan, MP; Ruparel, NB, 2009
)
0.35
" For constipation, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, morphine produced a bell-shaped dose-response curve, whereas DPDPE and U69,593 were inactive."( In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile.
Kuo, A; Meutermans, W; Smith, MT; Wyse, BD, 2015
)
0.42
"First, a dose-response curve for analgesic efficacy was generated for each opioid agonist."( Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury.
Aceves, M; Hook, MA; Mathai, BB, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
delta-opioid receptor agonistnull
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
heterodetic cyclic peptideA heterodetic cyclic peptide is a peptide consisting only of amino-acid residues, but in which the linkages forming the ring are not solely peptide bonds; one or more is an isopeptide, disulfide, ester, or other bond.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (11)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Cytosol aminopeptidaseSus scrofa (pig)Ki0.00170.00020.00220.0046AID1630712
Delta-type opioid receptorRattus norvegicus (Norway rat)Ki0.00230.00000.60689.2330AID1689584
Mu-type opioid receptorRattus norvegicus (Norway rat)Ki0.30530.00000.38458.6000AID1798045
Mu-type opioid receptorHomo sapiens (human)IC50 (µMol)0.00160.00010.813310.0000AID1630481
Mu-type opioid receptorHomo sapiens (human)Ki10.00000.00000.419710.0000AID307013
Delta-type opioid receptorHomo sapiens (human)IC50 (µMol)0.00110.00020.75218.0140AID1336342; AID1425957; AID1630496
Delta-type opioid receptorHomo sapiens (human)Ki0.07590.00000.59789.9300AID1355419; AID1434274; AID1581725; AID1630478; AID1630712; AID1798045; AID1820170; AID307014
Kappa-type opioid receptorCavia porcellus (domestic guinea pig)Ki0.30530.00000.20186.4240AID1798045
Kappa-type opioid receptorHomo sapiens (human)Ki10.00000.00000.362410.0000AID307015
Cannabinoid receptor 1Mus musculus (house mouse)Ki0.00170.00060.72467.2000AID1630712
Mu-type opioid receptorCavia porcellus (domestic guinea pig)Ki0.00170.00000.27869.0000AID1630712
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gastrin/cholecystokinin type B receptorHomo sapiens (human)Kd0.00050.00050.00530.0217AID1798046
Delta-type opioid receptorMus musculus (house mouse)EC50 (µMol)0.01000.00110.40144.8000AID1629760
Delta-type opioid receptorRattus norvegicus (Norway rat)EC50 (µMol)0.18470.00050.36496.9000AID1456297; AID1689595
Mu-type opioid receptorRattus norvegicus (Norway rat)Kd0.00050.00021.296510.0000AID1798026; AID1798042; AID1798046
Delta-type opioid receptorHomo sapiens (human)EC50 (µMol)0.01040.00000.43328.3000AID1237282; AID1262271; AID1275490; AID1279233; AID1303080; AID1812978; AID1820696; AID1888743; AID307018
Delta-type opioid receptorHomo sapiens (human)Kd0.00050.00040.51471.9800AID1798026; AID1798042; AID1798046
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (60)

Processvia Protein(s)Taxonomy
gastric acid secretionGastrin/cholecystokinin type B receptorHomo sapiens (human)
cell surface receptor signaling pathwayGastrin/cholecystokinin type B receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayGastrin/cholecystokinin type B receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationGastrin/cholecystokinin type B receptorHomo sapiens (human)
positive regulation of cell population proliferationGastrin/cholecystokinin type B receptorHomo sapiens (human)
cholecystokinin signaling pathwayGastrin/cholecystokinin type B receptorHomo sapiens (human)
pH reductionGastrin/cholecystokinin type B receptorHomo sapiens (human)
digestive tract developmentGastrin/cholecystokinin type B receptorHomo sapiens (human)
gland developmentGastrin/cholecystokinin type B receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMu-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
sensory perceptionMu-type opioid receptorHomo sapiens (human)
negative regulation of cell population proliferationMu-type opioid receptorHomo sapiens (human)
sensory perception of painMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
behavioral response to ethanolMu-type opioid receptorHomo sapiens (human)
positive regulation of neurogenesisMu-type opioid receptorHomo sapiens (human)
negative regulation of Wnt protein secretionMu-type opioid receptorHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeMu-type opioid receptorHomo sapiens (human)
calcium ion transmembrane transportMu-type opioid receptorHomo sapiens (human)
cellular response to morphineMu-type opioid receptorHomo sapiens (human)
regulation of cellular response to stressMu-type opioid receptorHomo sapiens (human)
regulation of NMDA receptor activityMu-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayMu-type opioid receptorHomo sapiens (human)
immune responseDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerDelta-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
adult locomotory behaviorDelta-type opioid receptorHomo sapiens (human)
negative regulation of gene expressionDelta-type opioid receptorHomo sapiens (human)
negative regulation of protein-containing complex assemblyDelta-type opioid receptorHomo sapiens (human)
positive regulation of CREB transcription factor activityDelta-type opioid receptorHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylationDelta-type opioid receptorHomo sapiens (human)
response to nicotineDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
eating behaviorDelta-type opioid receptorHomo sapiens (human)
regulation of mitochondrial membrane potentialDelta-type opioid receptorHomo sapiens (human)
regulation of calcium ion transportDelta-type opioid receptorHomo sapiens (human)
cellular response to growth factor stimulusDelta-type opioid receptorHomo sapiens (human)
cellular response to hypoxiaDelta-type opioid receptorHomo sapiens (human)
cellular response to toxic substanceDelta-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayDelta-type opioid receptorHomo sapiens (human)
immune responseKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
chemical synaptic transmissionKappa-type opioid receptorHomo sapiens (human)
sensory perceptionKappa-type opioid receptorHomo sapiens (human)
locomotory behaviorKappa-type opioid receptorHomo sapiens (human)
sensory perception of painKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
response to insulinKappa-type opioid receptorHomo sapiens (human)
positive regulation of dopamine secretionKappa-type opioid receptorHomo sapiens (human)
negative regulation of luteinizing hormone secretionKappa-type opioid receptorHomo sapiens (human)
response to nicotineKappa-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
maternal behaviorKappa-type opioid receptorHomo sapiens (human)
eating behaviorKappa-type opioid receptorHomo sapiens (human)
response to estrogenKappa-type opioid receptorHomo sapiens (human)
estrous cycleKappa-type opioid receptorHomo sapiens (human)
response to ethanolKappa-type opioid receptorHomo sapiens (human)
regulation of saliva secretionKappa-type opioid receptorHomo sapiens (human)
behavioral response to cocaineKappa-type opioid receptorHomo sapiens (human)
sensory perception of temperature stimulusKappa-type opioid receptorHomo sapiens (human)
defense response to virusKappa-type opioid receptorHomo sapiens (human)
cellular response to lipopolysaccharideKappa-type opioid receptorHomo sapiens (human)
cellular response to glucose stimulusKappa-type opioid receptorHomo sapiens (human)
positive regulation of p38MAPK cascadeKappa-type opioid receptorHomo sapiens (human)
positive regulation of potassium ion transmembrane transportKappa-type opioid receptorHomo sapiens (human)
response to acrylamideKappa-type opioid receptorHomo sapiens (human)
positive regulation of eating behaviorKappa-type opioid receptorHomo sapiens (human)
conditioned place preferenceKappa-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayKappa-type opioid receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (17)

Processvia Protein(s)Taxonomy
cholecystokinin receptor activityGastrin/cholecystokinin type B receptorHomo sapiens (human)
protein bindingGastrin/cholecystokinin type B receptorHomo sapiens (human)
gastrin receptor activityGastrin/cholecystokinin type B receptorHomo sapiens (human)
peptide hormone bindingGastrin/cholecystokinin type B receptorHomo sapiens (human)
type B gastrin/cholecystokinin receptor bindingGastrin/cholecystokinin type B receptorHomo sapiens (human)
1-phosphatidylinositol-3-kinase regulator activityGastrin/cholecystokinin type B receptorHomo sapiens (human)
G-protein alpha-subunit bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled receptor activityMu-type opioid receptorHomo sapiens (human)
beta-endorphin receptor activityMu-type opioid receptorHomo sapiens (human)
voltage-gated calcium channel activityMu-type opioid receptorHomo sapiens (human)
protein bindingMu-type opioid receptorHomo sapiens (human)
morphine receptor activityMu-type opioid receptorHomo sapiens (human)
G-protein beta-subunit bindingMu-type opioid receptorHomo sapiens (human)
neuropeptide bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityDelta-type opioid receptorHomo sapiens (human)
protein bindingDelta-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled enkephalin receptor activityDelta-type opioid receptorHomo sapiens (human)
neuropeptide bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityKappa-type opioid receptorHomo sapiens (human)
protein bindingKappa-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingKappa-type opioid receptorHomo sapiens (human)
dynorphin receptor activityKappa-type opioid receptorHomo sapiens (human)
neuropeptide bindingKappa-type opioid receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (24)

Processvia Protein(s)Taxonomy
plasma membraneGastrin/cholecystokinin type B receptorHomo sapiens (human)
intracellular membrane-bounded organelleGastrin/cholecystokinin type B receptorHomo sapiens (human)
plasma membraneGastrin/cholecystokinin type B receptorHomo sapiens (human)
endosomeMu-type opioid receptorHomo sapiens (human)
endoplasmic reticulumMu-type opioid receptorHomo sapiens (human)
Golgi apparatusMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
axonMu-type opioid receptorHomo sapiens (human)
dendriteMu-type opioid receptorHomo sapiens (human)
perikaryonMu-type opioid receptorHomo sapiens (human)
synapseMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
neuron projectionMu-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneDelta-type opioid receptorHomo sapiens (human)
dendrite membraneDelta-type opioid receptorHomo sapiens (human)
presynaptic membraneDelta-type opioid receptorHomo sapiens (human)
axon terminusDelta-type opioid receptorHomo sapiens (human)
spine apparatusDelta-type opioid receptorHomo sapiens (human)
postsynaptic density membraneDelta-type opioid receptorHomo sapiens (human)
neuronal dense core vesicleDelta-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
neuron projectionDelta-type opioid receptorHomo sapiens (human)
nucleoplasmKappa-type opioid receptorHomo sapiens (human)
mitochondrionKappa-type opioid receptorHomo sapiens (human)
cytosolKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
membraneKappa-type opioid receptorHomo sapiens (human)
sarcoplasmic reticulumKappa-type opioid receptorHomo sapiens (human)
T-tubuleKappa-type opioid receptorHomo sapiens (human)
dendriteKappa-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneKappa-type opioid receptorHomo sapiens (human)
presynaptic membraneKappa-type opioid receptorHomo sapiens (human)
perikaryonKappa-type opioid receptorHomo sapiens (human)
axon terminusKappa-type opioid receptorHomo sapiens (human)
postsynaptic membraneKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
neuron projectionKappa-type opioid receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (73)

Assay IDTitleYearJournalArticle
AID1303080Agonist activity at human DOR expressed in CHO cell membranes after 60 mins by [35S]GTP-gamma-S binding assay2016ACS medicinal chemistry letters, Apr-14, Volume: 7, Issue:4
Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
AID1629760Agonist activity at mouse delta opioid receptor-1 expressed in CHO cell membranes assessed as [35S]GTPgammaS binding incubated for 60 mins by scintillation spectroscopic analysis2016Journal of medicinal chemistry, 09-22, Volume: 59, Issue:18
Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2.
AID1427697Displacement of [3H]lleDelt2 from delta opioid receptor in Wistar rat brain membranes after 45 mins by liquid scintillation counting method2017ACS medicinal chemistry letters, Apr-13, Volume: 8, Issue:4
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.
AID1689599Agonist activity at human kappa opioid receptor expressed in CHO cells incubated for 1 hr by [35S]GTPgammaS binding based liquid scintillation counting method relative to control2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1630497Agonist activity at human DOR expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by EIA method relative to control2016Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19
Versatile Picklocks To Access All Opioid Receptors: Tuning the Selectivity and Functional Profile of the Cyclotetrapeptide c[Phe-d-Pro-Phe-Trp] (CJ-15,208).
AID1456297Agonist activity at rat delta opioid receptor expressed in rat C6 cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 1 hr by liquid scintillation counting method2017Bioorganic & medicinal chemistry, 04-15, Volume: 25, Issue:8
Modulation of opioid receptor affinity and efficacy via N-substitution of 9β-hydroxy-5-(3-hydroxyphenyl)morphan: Synthesis and computer simulation study.
AID1812974Agonist activity at MOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competiti2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1427703Analgesic activity in CD-1 mouse model of formalin-induced pain assessed as increase in latency to respond with hind paw lick or biting at 150 nmol/mouse, sc administered 15 mins prior to formalin injection measured up to 40 mins post dose2017ACS medicinal chemistry letters, Apr-13, Volume: 8, Issue:4
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.
AID1812978Agonist activity at DOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competiti2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1820166Displacement of [3H]-PrRP-20 from human PrRP receptor expressed in CHO cells by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1629787Antinociceptive activity in CD-1 mouse assessed as increase in reaction time at 10 ug, icv administered on day 6 after DOR1-exon3 antisense oligodeoxynucleotide injection on day 1, 3 and 5 by radiant heat tail flick assay2016Journal of medicinal chemistry, 09-22, Volume: 59, Issue:18
Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2.
AID1427702Antinociceptive activity in CD-1 mouse model of thermal-induced nociception assessed as increase in latency to tail withdrawal at 23 nmol/mouse, icv measured 45 mins post dose by tail flick test2017ACS medicinal chemistry letters, Apr-13, Volume: 8, Issue:4
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.
AID1425957Agonist activity at human DOR expressed in HEK293 cells assessed as inhibition of forskolin-induced adenylyl cyclase-mediated cAMP accumulation after 30 mins by HTRF assay2017European journal of medicinal chemistry, Jan-27, Volume: 126Discovery, structure-activity relationship studies, and anti-nociceptive effects of N-(1,2,3,4-tetrahydro-1-isoquinolinylmethyl)benzamides as novel opioid receptor agonists.
AID1581726Displacement of [3H]U69,593 from human recombinant kappa opioid receptor expressed in rat RBL cell membranes incubated for 60 mins2020Journal of medicinal chemistry, 01-09, Volume: 63, Issue:1
Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids.
AID1812976Agonist activity at KOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competiti2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1820167Displacement of [125I]-Kp-10 from human Kiss1 receptor by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1275485Agonist activity at human recombinant KOR expressed in CHO cells assessed as calcium mobilization up to 1 uM by Fluo-4 AM based fluorescence analysis2016European journal of medicinal chemistry, Feb-15, Volume: 109Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.
AID1262271Agonist activity at human delta opioid receptor over-expressed in CHO cell membrane after 1 hr by [35S]GTPgammaS binding assay2015Bioorganic & medicinal chemistry letters, Dec-01, Volume: 25, Issue:23
A selective delta opioid receptor antagonist based on a stilbene core.
AID1275487Agonist activity at human recombinant MOR expressed in CHO cells assessed as calcium mobilization up to 1 uM by Fluo-4 AM based fluorescence analysis2016European journal of medicinal chemistry, Feb-15, Volume: 109Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.
AID1689596Agonist activity at human kappa opioid receptor expressed in CHO cells incubated for 1 hr by [35S]GTPgammaS binding based liquid scintillation counting method2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1630478Displacement of [3H]diprenorphine from human DOR expressed in HEK293 cell membranes incubated for 90 mins by liquid scintillation counting2016Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19
Versatile Picklocks To Access All Opioid Receptors: Tuning the Selectivity and Functional Profile of the Cyclotetrapeptide c[Phe-d-Pro-Phe-Trp] (CJ-15,208).
AID1237282Inverse agonist activity at human DOR expressed in CHO cell membranes by [35S]GTPgammaS binding assay2015Bioorganic & medicinal chemistry letters, Aug-01, Volume: 25, Issue:15
Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists.
AID1820171Displacement of [3H]-Diprenorphine from human KOP receptor expressed in HEK293 cells by scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1279237Agonist activity at human recombinant KOR expressed in CHO cells at 1 uM by calcium mobilization assay2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID307014Displacement of [3H]diprenorphine from human cloned delta opioid receptor2007Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9
Further studies of tyrosine surrogates in opioid receptor peptide ligands.
AID1888743Agonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 2 hrs by scintillation counting method2022Bioorganic & medicinal chemistry, 01-01, Volume: 53Morphinan derivatives with an oxabicyclo[3.2.1]octane structure as dual agonists toward δ and κ opioid receptors.
AID1427701Antinociceptive activity in CD-1 mouse model of thermal-induced nociception assessed as increase in latency to respond with hind paw lick or jumping at 23 nmol/mouse, icv measured 45 mins post dose by hot plate test2017ACS medicinal chemistry letters, Apr-13, Volume: 8, Issue:4
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.
AID1820696Agonist activity at human delta opioid receptor expressed in HEK293 assessed as increase in calcium mobilization incubated for 60 mins by FLIPR assay
AID1630718Selectivity ratio of Ki for displacement of [3H]DPDPE from human DOR expressed in CHO cells to Ki for displacement of [3H]DAMGO from MOR in HEK293 cells2016Bioorganic & medicinal chemistry, 11-01, Volume: 24, Issue:21
An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.
AID1299238Agonist activity at DOR in CD1 mouse vas deferens assessed as inhibition of EFS-induced contractions incubated for 60 mins2016Bioorganic & medicinal chemistry, 06-15, Volume: 24, Issue:12
Evaluation of N-substituent structural variations in opioid receptor profile of LP1.
AID1689595Agonist activity at rat delta opioid receptor expressed in CHO cells incubated for 1 hr by [35S]GTPgammaS binding based liquid scintillation counting method2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1427698Displacement of [3H]DAMGO from mu opioid receptor in Wistar rat brain membranes after 45 mins by liquid scintillation counting method2017ACS medicinal chemistry letters, Apr-13, Volume: 8, Issue:4
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.
AID1630710Displacement of [3H]DAMGO from MOR in HEK293 cells2016Bioorganic & medicinal chemistry, 11-01, Volume: 24, Issue:21
An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.
AID1630496Agonist activity at human DOR expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by EIA method2016Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19
Versatile Picklocks To Access All Opioid Receptors: Tuning the Selectivity and Functional Profile of the Cyclotetrapeptide c[Phe-d-Pro-Phe-Trp] (CJ-15,208).
AID1689594Agonist activity at rat mu opioid receptor expressed in CHO cells incubated for 1 hr by [35S]GTPgammaS binding based liquid scintillation counting method2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1812979Agonist activity at DOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competiti2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1285645Displacement of [3H]DADLE from human recombinant delta-type 2 opioid receptor expressed in CHO cells2016Bioorganic & medicinal chemistry, Apr-15, Volume: 24, Issue:8
Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents.
AID1275490Agonist activity at human recombinant DOR expressed in CHO cells assessed as calcium mobilization by Fluo-4 AM based fluorescence analysis2016European journal of medicinal chemistry, Feb-15, Volume: 109Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.
AID1820169Displacement of [3H]-Diprenorphine from human MOP receptor expressed in HEK293 cells by scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1630482Agonist activity at human MOR expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by EIA method relative to control2016Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19
Versatile Picklocks To Access All Opioid Receptors: Tuning the Selectivity and Functional Profile of the Cyclotetrapeptide c[Phe-d-Pro-Phe-Trp] (CJ-15,208).
AID1812977Agonist activity at KOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation by measuring maximal efficacy preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and 2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID307013Displacement of [3H]diprenorphine from human cloned mu opioid receptor2007Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9
Further studies of tyrosine surrogates in opioid receptor peptide ligands.
AID1812975Agonist activity at MOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation by measuring maximal efficacy preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and 2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-Lasting, and Peripherally Restricted Antinociception with Diminished Side Effects.
AID1630711Displacement of [3H]U69593 from rat KOR expressed in CHO cells2016Bioorganic & medicinal chemistry, 11-01, Volume: 24, Issue:21
An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.
AID307017Agonist activity at human cloned mu opioid receptor assessed as stimulation of [35S]GTPgammaS binding2007Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9
Further studies of tyrosine surrogates in opioid receptor peptide ligands.
AID1630481Agonist activity at human MOR expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by EIA method2016Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19
Versatile Picklocks To Access All Opioid Receptors: Tuning the Selectivity and Functional Profile of the Cyclotetrapeptide c[Phe-d-Pro-Phe-Trp] (CJ-15,208).
AID1820172Displacement of [3H]nociceptin from human recombinant NOP receptor expressed in HEK293 cells by scintillation counting analysis2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1427699Selectivity index, ratio of Ki for mu opioid receptor in Wistar rat brain membranes to Ki for delta opioid receptor in Wistar rat brain membranes2017ACS medicinal chemistry letters, Apr-13, Volume: 8, Issue:4
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.
AID307015Displacement of [3H]diprenorphine from human cloned kappa opioid receptor2007Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9
Further studies of tyrosine surrogates in opioid receptor peptide ligands.
AID1279235Agonist activity at human recombinant MOR expressed in CHO cells at 1 uM by calcium mobilization assay2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID1336342Displacement of [3H]DADLE from human recombinant delta opioid receptor expressed in CHO cells measured after 120 mins by scintillation counting method2017Bioorganic & medicinal chemistry, 01-15, Volume: 25, Issue:2
Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH
AID1689584Displacement of [3H]-DPDPE from rat delta opioid receptor expressed in CHO cells incubated for 30 mins by liquid scintillation counting method2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1434274Displacement of [3H]DPDPE from human DOR expressed in CHO cells2017Bioorganic & medicinal chemistry letters, 02-01, Volume: 27, Issue:3
Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands.
AID307018Agonist activity at human cloned delta opioid receptor assessed as stimulation of [35S]GTP-gamma-S binding2007Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9
Further studies of tyrosine surrogates in opioid receptor peptide ligands.
AID1581725Displacement of [3H]DADLE from human recombinant delta opioid receptor expressed in rat Chem-1 (RBL) cell membranes incubated for 60 mins2020Journal of medicinal chemistry, 01-09, Volume: 63, Issue:1
Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids.
AID1237283Inverse agonist activity at human DOR expressed in CHO cell membranes by [35S]GTPgammaS binding assay relative to control2015Bioorganic & medicinal chemistry letters, Aug-01, Volume: 25, Issue:15
Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists.
AID1456284Agonist activity at rat delta opioid receptor expressed in rat C6 cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 1 hr by liquid scintillation counting method relative to DPDPE2017Bioorganic & medicinal chemistry, 04-15, Volume: 25, Issue:8
Modulation of opioid receptor affinity and efficacy via N-substitution of 9β-hydroxy-5-(3-hydroxyphenyl)morphan: Synthesis and computer simulation study.
AID1689597Agonist activity at rat mu opioid receptor expressed in CHO cells incubated for 1 hr by [35S]GTPgammaS binding based liquid scintillation counting method relative to control2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1581727Displacement of [3H]DAMGO from human recombinant mu opioid receptor expressed in HEK293 cell membranes incubated for 60 mins2020Journal of medicinal chemistry, 01-09, Volume: 63, Issue:1
Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids.
AID1630712Displacement of [3H]DPDPE from human DOR expressed in CHO cells2016Bioorganic & medicinal chemistry, 11-01, Volume: 24, Issue:21
An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.
AID1820170Displacement of [3H]-Diprenorphine from human DOP receptor expressed in HEK293 cells by scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1355419Displacement of [3H]diprenorphine from human delta opioid receptor expressed in HEK293 cell membranes after 2 hrs by liquid scintillation spectrometry2018Journal of medicinal chemistry, 07-12, Volume: 61, Issue:13
Constraining Endomorphin-1 by β,α-Hybrid Dipeptide/Heterocycle Scaffolds: Identification of a Novel κ-Opioid Receptor Selective Partial Agonist.
AID1820168Displacement of [125I]-43RFa from human QRFP receptor expressed in CHO cells by TopCount scintillation counting method2021Journal of medicinal chemistry, 06-10, Volume: 64, Issue:11
Identification of an
AID1630716Selectivity ratio of Ki for displacement of [3H]U69593 from rat KOR expressed in CHO cells to Ki for displacement of [3H]DAMGO from MOR in HEK293 cells2016Bioorganic & medicinal chemistry, 11-01, Volume: 24, Issue:21
An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.
AID1689598Agonist activity at rat delta opioid receptor expressed in CHO cells incubated for 1 hr by [35S]GTPgammaS binding based liquid scintillation counting method relative to control2020European journal of medicinal chemistry, Mar-01, Volume: 189Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic.
AID1279233Agonist activity at human recombinant DOR expressed in CHO cells by calcium mobilization assay2016Bioorganic & medicinal chemistry, Apr-01, Volume: 24, Issue:7
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
AID1346373Mouse delta receptor (Opioid receptors)1994Molecular pharmacology, Feb, Volume: 45, Issue:2
Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.
AID1346361Human delta receptor (Opioid receptors)1998NIDA research monograph, Mar, Volume: 178Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.
AID1346361Human delta receptor (Opioid receptors)1983Proceedings of the National Academy of Sciences of the United States of America, Oct, Volume: 80, Issue:19
Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors.
AID1798046Radioligand Labeled Binding Assay and [35S]GTP-gamma-S Binding Assay from Article 10.1021/jm050921q: \\Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.\\2006Journal of medicinal chemistry, May-18, Volume: 49, Issue:10
Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.
AID1798045Radioligand Labeled Binding Assay from Article 10.1021/jm061048b: \\Synthesis of Stable and Potent delta/mu Opioid Peptides: Analogues of H-Tyr-c[d-Cys-Gly-Phe-d-Cys]-OH by Ring-Closing Metathesis.\\2007Journal of medicinal chemistry, Jun-28, Volume: 50, Issue:13
Synthesis of stable and potent delta/mu opioid peptides: analogues of H-Tyr-c[D-Cys-Gly-Phe-D-Cys]-OH by ring-closing metathesis.
AID1798042Radioligand Labeled Binding Assay and [35S]GTP-gamma-S Binding Assay from Article 10.1021/jm061465o: \\Development of novel enkephalin analogues that have enhanced opioid activities at both mu and delta opioid receptors.\\2007Journal of medicinal chemistry, Nov-01, Volume: 50, Issue:22
Development of novel enkephalin analogues that have enhanced opioid activities at both mu and delta opioid receptors.
AID1798026Radioligand Labeled Binding Assay and [35S]GTP-gamma-S Binding Assay from Article 10.1021/jm070332f: \\A Structure-Activity Relationship Study and Combinatorial Synthetic Approach of C-Terminal Modified Bifunctional Peptides That Are delta/mu Opioid Recept2008Journal of medicinal chemistry, Mar-13, Volume: 51, Issue:5
A structure-activity relationship study and combinatorial synthetic approach of C-terminal modified bifunctional peptides that are delta/mu opioid receptor agonists and neurokinin 1 receptor antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,268)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990156 (12.30)18.7374
1990's742 (58.52)18.2507
2000's285 (22.48)29.6817
2010's76 (5.99)24.3611
2020's9 (0.71)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 7.68

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index7.68 (24.57)
Research Supply Index7.18 (2.92)
Research Growth Index4.86 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (7.68)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews5 (0.38%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other1,309 (99.62%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]