clocinnamox: structure given in first source; an opioid mu receptor agonist [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 6540640 |
| CHEMBL ID | 386492 |
| SCHEMBL ID | 20573715 |
| MeSH ID | M0206426 |
| Synonym |
|---|
| clocinnamox |
| bdbm50195656 |
| c-cam |
| CHEMBL386492 , |
| 14beta-4'-chlorocinnamoylaminodihydronormorphinone |
| (2e)-3-(4-chlorophenyl)-n-[(1r,13r,17s)-4-(cyclopropylmethyl)-10-hydroxy-14-oxo-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18)-trien-17-yl]prop-2-enamide |
| bdbm50066535 |
| 14beta-4''-chlorocinnamoylaminodihydronormorphinone |
| 1n-[4-cyclopropylmethyl-10-hydroxy-14-oxo-(17s)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7,9,11(18)-trien-17-yl]-3-(4-chlorophenyl)-(e)-2-propenamide(clocinnamox (c-cam)) |
| SCHEMBL20573715 |
| Q15634049 |
Clocinnamox eliminated morphine's antinociceptive effects at doses up to 1000 mg/kg for at least seven days. The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine.
| Excerpt | Relevance | Reference |
|---|---|---|
| " produced an acute rightward shift of the dose-response curves of the selective mu opioid agonists alfentanil and morphine at all tested temperatures." | ( In vivo determination of mu opioid receptor turnover in rhesus monkeys after irreversible blockade with clocinnamox. Butelman, ER; Lewis, JW; Walker, EA; Woods, JH; Zernig, G, 1994) | 0.29 |
| " Fentanyl pumps and placebo pellets were removed on the third day following implantation and 4 h later mu-opioid receptor saturation binding studies in whole brain ([3H][D-Ala2,MePhe4,Gly-ol5]enkephalin: DAMGO) or fentanyl analgesic dose-response studies (tailflick assay) were conducted." | ( Magnitude of tolerance to fentanyl is independent of mu-opioid receptor density. Chan, KW; Duttory, A; Yoburn, BC, 1997) | 0.3 |
| " At 1 mg/kg, CCAM caused a 300-fold shift of the alfentanil dose-response curve and also depressed the maximum response rates." | ( Clocinnamox inhibits the intravenous self-administration of opioid agonists in rhesus monkeys: comparison with effects on opioid agonist-mediated antinociception. Lewis, JW; Woods, JH; Zernig, G, 1997) | 0.3 |
| "0 mg/kg clocinnamox displaced the morphine dose-response curve 4-fold to the right of the control curve and 10 mg/kg clocinnamox eliminated morphine's antinociceptive effects at doses up to 1000 mg/kg for at least seven days." | ( Clocinnamox dose-dependently antagonizes morphine-analgesia and [3H]DAMGO binding in rats. Paronis, CA; Woods, JH, 1997) | 0.3 |
| "8 mg/kg) produced a 74-fold increase in the ED(50) of morphine while showing no effect on bremazocine or BW373U86 dose-response curves." | ( Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine. Broadbear, JH; Burke, TF; Husbands, SM; Lewis, JW; Sumpter, TL; Traynor, JR; Woods, JH, 2000) | 0.31 |
| " Clocinnamox (10 mg/kg) produced a 7- and 12-fold further decrease in morphine and fentanyl potency, respectively, a reduction in the slope of the morphine dose-response curve, and a suppression of the maximal morphine responding for buprenorphine." | ( Clocinnamox distinguishes opioid agonists according to relative efficacy in normal and morphine-treated rats trained to discriminate morphine. Walker, EA; Young, AM, 2002) | 0.31 |
| " The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine and the highest dose of clocinnamox reduced the maximal effect of morphine and oxycodone, but not etorphine." | ( Opioid agonist efficacy predicts the magnitude of tolerance and the regulation of mu-opioid receptors and dynamin-2. Kumar, P; Pawar, M; Sirohi, S; Sunkaraneni, S; Walker, EA; Yoburn, BC, 2007) | 0.34 |
| " hydromorphone's time of peak analgesic (tail-flick) effect (45 min) and ED50 using standard and cumulative dosing protocols (0." | ( Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation. Dighe, SV; Kumar, P; Sirohi, S; Sunkaraneni, S; Walker, EA; Yoburn, BC, 2008) | 0.35 |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Delta-type opioid receptor | Mus musculus (house mouse) | Ki | 0.0027 | 0.0000 | 0.5393 | 9.4000 | AID395294 |
| Mu-type opioid receptor | Homo sapiens (human) | IC50 (µMol) | 0.0005 | 0.0001 | 0.8133 | 10.0000 | AID273141 |
| Mu-type opioid receptor | Homo sapiens (human) | Ki | 0.0030 | 0.0000 | 0.4197 | 10.0000 | AID269569; AID273130; AID395293; AID437718 |
| Delta-type opioid receptor | Homo sapiens (human) | IC50 (µMol) | 0.0002 | 0.0002 | 0.7521 | 8.0140 | AID273143 |
| Delta-type opioid receptor | Homo sapiens (human) | Ki | 0.0025 | 0.0000 | 0.5978 | 9.9300 | AID269569; AID269571; AID273131; AID273132; AID395294; AID437719 |
| Kappa-type opioid receptor | Cavia porcellus (domestic guinea pig) | Ki | 0.0027 | 0.0000 | 0.2018 | 6.4240 | AID269571 |
| Kappa-type opioid receptor | Homo sapiens (human) | IC50 (µMol) | 0.0001 | 0.0000 | 1.2011 | 10.0000 | AID273145 |
| Kappa-type opioid receptor | Homo sapiens (human) | Ki | 0.0014 | 0.0000 | 0.3624 | 10.0000 | AID269573; AID273131; AID395295; AID437720 |
| Mu-type opioid receptor | Mus musculus (house mouse) | Ki | 0.0030 | 0.0000 | 0.1228 | 1.3000 | AID395293 |
| Mu-type opioid receptor | Cavia porcellus (domestic guinea pig) | Ki | 0.0027 | 0.0000 | 0.2786 | 9.0000 | AID273132 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Mu-type opioid receptor | Homo sapiens (human) | Ke | 0.0005 | 0.0000 | 0.2488 | 3.0700 | AID269581; AID395299; AID437721 |
| Delta-type opioid receptor | Homo sapiens (human) | Ke | 0.0002 | 0.0001 | 0.6979 | 9.0700 | AID269582; AID395300; AID437722 |
| Kappa-type opioid receptor | Homo sapiens (human) | Ke | 0.0001 | 0.0000 | 0.3540 | 5.8100 | AID269583; AID395301; AID437723 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID149815 | In vitro binding affinity against Opioid receptor delta 1 (DPDPE) in rat brain homogenates. | 1998 | Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18 | 3-Alkyl ethers of clocinnamox: delayed long-term mu-antagonists with variable mu efficacy. |
| AID269583 | Reversal of stimulation of [35S]GTPgammaS binding to human recombinant KOR transfected in CHO cells relative to U69593 | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID395301 | Antagonist activity against human kappa opioid receptor expressed in CHO cells assessed as inhibition of U69593-induced [35S]GTPgammaS binding | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | 14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. |
| AID269571 | Displacement of [3H]Cl-DPDPE from human recombinant DOR expressed in CHO cells | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID269597 | Antagonist activity against morphine-induced antinociception in sc dosed mouse by hot water tail withdrawal assay at 32 mg/kg, sc | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID395294 | Displacement of [3H]DPDPE from human delta opioid receptor expressed in CHO cells | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | 14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. |
| AID273133 | Selectivity for human mu opioid receptor over delta opioid receptor | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID269594 | Agonist activity in mouse by hot water tail withdrawal assay at 32 mg/kg, sc | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID437721 | Antagonist activity at human mu opioid receptor expressed in CHO cells assessed as inhibition of DAMGO-induced [35S]GTPgammaS binding | 2009 | Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21 | 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists. |
| AID151768 | In vitro binding affinity against Opioid receptor mu 1 (DAMGO) opioid receptor in rat brain homogenates. | 1998 | Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18 | 3-Alkyl ethers of clocinnamox: delayed long-term mu-antagonists with variable mu efficacy. |
| AID273145 | Activity at human recombinant kappa opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID269581 | Reversal of stimulation of [35S]GTP-gamma-S binding to human recombinant MOR transfected in CHO cells relative to DAMGO | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID437723 | Antagonist activity at human kappa opioid receptor expressed in CHO cells assessed as inhibition of U69593-induced [35S]GTPgammaS binding | 2009 | Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21 | 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists. |
| AID273132 | Displacement of [3H]Cl-DPDPE from human recombinant delta opioid receptor expressed in CHO cells | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID395295 | Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cells | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | 14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. |
| AID273142 | Activity at human recombinant mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding relative to DAMGO | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID437718 | Displacement of [3H]DAMGO from human recombinant mu opioid receptor expressed in CHO cells by liquid scintillation counting | 2009 | Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21 | 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists. |
| AID149363 | Displacement of radioligand [3H]- DPDPE on Opioid receptor delta 1 in monkey brain membranes | 2000 | Journal of medicinal chemistry, Aug-24, Volume: 43, Issue:17 | 3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist lacking a phenolic hydroxyl group. |
| AID273130 | Displacement of [3H]DAMGO from human recombinant mu opioid receptor expressed in CHO cells | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID437719 | Displacement of [3H]DPDPE from human recombinant delta opioid receptor expressed in CHO cells by liquid scintillation counting | 2009 | Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21 | 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists. |
| AID273141 | Activity at human recombinant mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID437722 | Antagonist activity at human delta opioid receptor expressed in CHO cells assessed as inhibition of DPDPE-induced [35S]GTPgammaS binding | 2009 | Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21 | 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists. |
| AID395299 | Antagonist activity against human mu opioid receptor expressed in CHO cells assessed as inhibition of DAMGO-induced [35S]GTPgammaS binding | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | 14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. |
| AID269590 | Agonist activity in mouse by phenylquinone abdominal stretching assay at 30 mg/kg, sc | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID269573 | Displacement of [3H]U-69593 from human recombinant KOR expressed in CHO cells | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID395300 | Antagonist activity against human delta opioid receptor expressed in CHO cells assessed as inhibition of DPDPE-induced [35S]GTPgammaS binding | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | 14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. |
| AID437720 | Displacement of [3H]U69593 from human recombinant kappa opioid receptor expressed in CHO cells by liquid scintillation counting | 2009 | Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21 | 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists. |
| AID273146 | Activity at human recombinant kappa opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding relative to U69593 | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID269587 | Agonist activity in sc dosed mouse by tail flick assay | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID149327 | Displacement of radioligand [3H]- DAMGO on Opioid receptor mu 1 in monkey brain membranes | 2000 | Journal of medicinal chemistry, Aug-24, Volume: 43, Issue:17 | 3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist lacking a phenolic hydroxyl group. |
| AID273131 | Displacement of [3H]U-69593 from human recombinant kappa opioid receptor expressed in CHO cells | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID148591 | In vitro binding affinity against Opioid receptor kappa 1 in rat brain homogenates. | 1998 | Journal of medicinal chemistry, Aug-27, Volume: 41, Issue:18 | 3-Alkyl ethers of clocinnamox: delayed long-term mu-antagonists with variable mu efficacy. |
| AID273147 | Inhibition of DAMGO-stimulated [35S]GTP-gamma-S binding to mu opioid receptor expressed in C6 cells at 100 nM | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID273143 | Activity at human recombinant delta opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID273134 | Selectivity for human mu opioid receptor over kappa opioid receptor | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID395293 | Displacement of [3H]DAMGO from human mu opioid receptor expressed in CHO cells | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | 14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. |
| AID269582 | Reversal of stimulation of [35S]GTP-gamma-S binding to human recombinant DOR transfected in CHO cells relative to DPDPE | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID149326 | Displacement of radioligand [35S]- GTPgammaS on Opioid receptor mu 1 in monkey brain membranes | 2000 | Journal of medicinal chemistry, Aug-24, Volume: 43, Issue:17 | 3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist lacking a phenolic hydroxyl group. |
| AID273144 | Activity at human recombinant delta opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding relative to DPDPE | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring. |
| AID269592 | Antagonist activity against morphine-induced antinociception in sc dosed mouse by tail flick assay | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| AID148135 | Displacement of radioligand [3H]- U-69,593 on Opioid receptor kappa 1 in monkey brain membranes | 2000 | Journal of medicinal chemistry, Aug-24, Volume: 43, Issue:17 | 3-Deoxyclocinnamox: the first high-affinity, nonpeptide mu-opioid antagonist lacking a phenolic hydroxyl group. |
| AID269569 | Displacement of [3H]DAMGO from human recombinant MOR expressed in CHO cells | 2006 | Journal of medicinal chemistry, Aug-24, Volume: 49, Issue:17 | Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 22 (45.83) | 18.2507 |
| 2000's | 20 (41.67) | 29.6817 |
| 2010's | 4 (8.33) | 24.3611 |
| 2020's | 2 (4.17) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 1 (2.08%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 47 (97.92%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||