Lofexidine is an α2-adrenergic agonist that has been used in the treatment of opioid withdrawal syndrome. It acts by stimulating α2-adrenergic receptors in the central nervous system, which leads to a decrease in the release of norepinephrine, a neurotransmitter that is involved in the symptoms of withdrawal. Lofexidine has been shown to be effective in reducing the severity of withdrawal symptoms, such as anxiety, restlessness, and insomnia. It is typically administered orally, and its effects usually begin within 1 to 2 hours. Lofexidine is generally well-tolerated, but it can cause side effects such as drowsiness, dry mouth, and dizziness. Lofexidine is not approved by the FDA for use in the United States. However, it is available in some other countries, such as the United Kingdom. The synthesis of lofexidine involves several steps, starting with the reaction of 2,6-dichlorobenzonitrile with 4-methoxy-3-nitroaniline. This is followed by a series of reactions including reduction, alkylation, and cyclization. Lofexidine is studied due to its potential to be a safer and more effective alternative to other treatments for opioid withdrawal, such as methadone and buprenorphine. Studies have shown that lofexidine may be particularly effective in patients who have a history of opioid dependence, as well as in patients who are at high risk for complications from opioid withdrawal.'
lofexidine: reduces narcotic withdrawal symptoms; RN given refers to parent cpd without isomeric designation; structure in Negwer, 5th ed, #6247 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 30668 |
| CHEMBL ID | 17860 |
| CHEBI ID | 51368 |
| SCHEMBL ID | 48960 |
| MeSH ID | M0085278 |
| Synonym |
|---|
| lofexidina |
| CHEBI:51368 , |
| 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1h-imidazole |
| lofexidinum |
| 2-{1-[(2,6-dichlorophenyl)oxy]ethyl}-4,5-dihydro-1h-imidazole |
| 31036-80-3 |
| lofexidinum [inn-latin] |
| 1h-imidazole, 2-(1-(2,6-dichlorophenoxy)ethyl)-4,5-dihydro- |
| 2-(1-(2,6-dichlorophenoxy)ethyl)-4,5-dihydro-1h-imidazole |
| 2-(alpha-(2,6-dichlorophenoxy)ethyl) delta-2-imidazoline |
| lofexidine [inn:ban] |
| lofexidina [inn-spanish] |
| 2-imidazoline 2-(1-(2,6-dichlorophenoxy)ethyl)- |
| lofexidine |
| 2-(alpha-(2,6-dichlorophenoxy)ethyl)2-imidazoline |
| DB04948 |
| HMS2090C03 |
| CHEMBL17860 , |
| lofexidine (inn) |
| D08141 |
| bdbm50019646 |
| 1h-imidazole, 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro- |
| ui82k0t627 , |
| unii-ui82k0t627 |
| 2-[1-(2,6-dichlorophenoxy)ethyl]-2-imidazoline |
| A820699 |
| FT-0670834 |
| FT-0670835 |
| FT-0627970 |
| AKOS015900265 |
| lofexidine [vandf] |
| lofexidine [mi] |
| lofexidine [who-dd] |
| 2-(1-(2,6-dichlorophenoxy)ethyl)-2-imidazoline |
| lofexidine [inn] |
| CCG-220521 |
| AB00698543-05 |
| SCHEMBL48960 |
| cas-31036-80-3 |
| NCGC00271513-02 |
| tox21_113963 |
| dtxsid7023221 , |
| dtxcid703221 |
| AB00698543-07 |
| (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene |
| KSMAGQUYOIHWFS-UHFFFAOYSA-N |
| (+)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene |
| AB00698543_09 |
| AB00698543_08 |
| J-507626 |
| SR-01000763628-4 |
| SR-01000763628-3 |
| sr-01000763628 |
| HMS3713J03 |
| gtpl9868 |
| ZB0288 |
| Q3836403 |
| baq-168;mdl-14042 |
| BCP30596 |
| lofexidinum pound>>britlofex |
| A51269 |
| 31036-80-3 (free base) |
| HY-B1052A |
| CS-0013650 |
| BS-22292 |
| EN300-7392995 |
| lofexidinum (inn-latin) |
| lofexidina (inn-spanish) |
| n07bc04 |
Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom for the treatment of opioid withdrawal symptoms. It is an effective and safe agent in treating symptoms related to opioid withdrawal in adults when compared with placebo. Although it is more widely accessible than other first-line therapies, its use in practice may be limited by cost.
Lofexidine has been shown to be effective in reducing the former and could potentially aid in recovery and withdrawal. L ofexidine would likely have been excluded for further development in this day and age given the existence and value of clonidine.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Lofexidine did not produce any observable side effects during or after treatment." | ( Differential effects of acute and chronic treatment with the α2-adrenergic agonist, lofexidine, on cocaine self-administration in rhesus monkeys. Fivel, PA; Kohut, SJ; Mello, NK, 2013) | 1.34 |
The lofexidine treatment more severe symptoms from day 3 to 7 and again on day 10 (the last day of treatment), but thereafter both groups showed a similar progressive symptom decline. Pretreatment with lofEXidine (0.05 mg/kg and 0.1mg/kg) attenuated stress-induced reinstatement of alcohol seeking.
| Excerpt | Reference | Relevance |
|---|---|---|
| "The lofexidine treatment more severe symptoms from day 3 to 7 and again on day 10 (the last day of treatment), but thereafter both groups showed a similar progressive symptom decline." | ( Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. Bearn, J; Gossop, M; Strang, J, 1996) | 1.05 |
| "Pretreatment with lofexidine (0.05 mg/kg and 0.1 mg/kg) attenuated stress-induced reinstatement of alcohol seeking and also decreased alcohol self-administration. " | ( Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats. Funk, D; Harding, S; Juzytsch, W; Lê, AD; Shaham, Y, 2005) | 0.66 |
Lofexidine significantly reduced opiate withdrawal symptoms without the adverse sedative and hypotensive effects that limit the safety and usefulness of clonidine. Clonidine caused adverse effects more frequently than did lfexidine.
The objective of this study was to characterize the clinical pharmacokinetic profile of lofexidine after oral delivery.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Lofexidine (LFX), an α2A adrenergic receptor agonist, known to alleviate opioid withdrawal symptoms, was assessed in combination with oral naltrexone (NTX) for effects on opioid use outcomes and NTX treatment compliance." | ( Lofexidine in Combination With Oral Naltrexone for Opioid Use Disorder Relapse Prevention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study. Fogelman, N; Hermes, G; Hyman, SM; Kosten, TR; Sinha, R, 2019) | 3.4 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Lofexidine is an orally bioavailable alpha 2-adrenergic receptor agonist analogue of clonidine that acts centrally to suppress opiate withdrawal symptoms." | ( Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis. Akerele, E; Al-Ghananeem, AM; Elkashef, A; Fischman, MW; Herman, BH; Kleber, H; Ling, W; Miotto, K; O'Brien, CP; Yu, E, 2008) | 1.55 |
Lofexidine, an alpha(2)-agonist, for opioid detoxification. 16 patients with primary hypertension who were receiving 50 mg hydrochlorothiazide twice a day while they were recumbent and upright and during isometric handgrip contraction.
| Excerpt | Relevance | Reference |
|---|---|---|
| " Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists." | ( Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists. Elko, EE; Jin, Y; Tran, T; Yorio, T, 1989) | 0.28 |
| " Hypotensive potency after intravenous administration to anesthetized, normotensive rats was determined as a measure of central alpha-adrenergic activity and expressed as pC25, obtained from log dose-response curves." | ( Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors. de Jonge, A; Lam, E; Slothorst-Grisdijk, FP; Timmermans, PB; van Meel, JC; van Zwieten, PA, 1981) | 0.26 |
| "We measured the first dosage effect and the long-term effect of lofexidine on blood pressure, heart rate, plasma catecholamines, and their major metabolites in 16 patients with primary hypertension who were receiving 50 mg hydrochlorothiazide twice a day while they were recumbent and upright and during isometric handgrip contraction." | ( Hemodynamic effect of lofexidine with a diuretic in hypertension. Alexander, N; Maronde, RF; Velasquez, M; Vlachakis, ND, 1983) | 0.82 |
| " Dosage regimens of clonidine must be individualized according to symptoms and side effects and closely supervised because of varying sensitivity to clonidine's sedative, hypotensive, and withdrawal-suppressing effects." | ( Clonidine in opiate withdrawal: review and appraisal of clinical findings. Resnick, RB; Washton, AM, ) | 0.13 |
| " In terms of lofexidine, there was no evidence of any adverse interactions with hydrochlorothiazide either following a single, oral administration to rats and mice or following short-term and long-term repeated oral dosing of rats and dogs." | ( Toxicology of the combination lofexidine/hydrochlorothiazide. Fontaine, R; Friehe, H; Gibson, JP; Larson, EJ; Sells, DM, 1982) | 0.92 |
| "Twenty eight opiate addicted inpatients who had been stabilised on methadone took part in a double-blind randomised trial of clonidine and lofexidine (14 on each treatment) for opiate detoxification: clonidine or lofexidine dosage was titrated according to symptoms." | ( Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Beckford, H; Kahn, A; Mumford, JP; Rogers, GA, 1997) | 0.81 |
| " Further benefit from lofexidine may be possible with revised dosing regimens." | ( Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal. Hu, WH; Lin, SK; Strang, J; Su, LW; Tsai, CJ, 1997) | 0.87 |
| "The objective of this study was to investigate lofexidine urine and plasma pharmacokinetics using three different dosing regimens in opioid dependent subjects." | ( Urine and plasma pharmacokinetics of lofexidine after oral delivery in opiate-dependent patients. Abbassi, M; Al Ghananeem, AM; Herman, BH; Ling, W; Miotto, K; Montgomery, A; O'Brien, CP; Walsh, R; Yu, E, 2009) | 0.88 |
| " The dosing regimens of lofexidine hydrochloride were ." | ( Urine and plasma pharmacokinetics of lofexidine after oral delivery in opiate-dependent patients. Abbassi, M; Al Ghananeem, AM; Herman, BH; Ling, W; Miotto, K; Montgomery, A; O'Brien, CP; Walsh, R; Yu, E, 2009) | 0.93 |
| "8 mg TID dosing regimens did not seem to be different at steady state (day 15)." | ( Urine and plasma pharmacokinetics of lofexidine after oral delivery in opiate-dependent patients. Abbassi, M; Al Ghananeem, AM; Herman, BH; Ling, W; Miotto, K; Montgomery, A; O'Brien, CP; Walsh, R; Yu, E, 2009) | 0.63 |
| "To review the pharmacology, toxicology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines for lofexidine, an alpha(2)-agonist, for opioid detoxification." | ( Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Gish, EC; Honey, BL; Johnson, PN; Miller, JL, 2010) | 2.01 |
| " Further large-scale controlled studies are needed to identify the safest, most effective dosage regimen required to achieve opioid detoxification." | ( Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Gish, EC; Honey, BL; Johnson, PN; Miller, JL, 2010) | 1.8 |
| Role | Description |
|---|---|
| alpha-adrenergic agonist | An agent that selectively binds to and activates alpha-adrenergic receptors. |
| antihypertensive agent | Any drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism. |
| [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] | |
| Class | Description |
|---|---|
| imidazoles | A five-membered organic heterocycle containing two nitrogen atoms at positions 1 and 3, or any of its derivatives; compounds containing an imidazole skeleton. |
| dichlorobenzene | Any member of the class of chlorobenzenes carrying two chloro groups at unspecified positions. |
| aromatic ether | Any ether in which the oxygen is attached to at least one aryl substituent. |
| carboxamidine | Compounds having the structure RC(=NR)NR2. The term is used as a suffix in systematic nomenclature to denote the -C(=NH)NH2 group including its carbon atom. |
| [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 | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| GLI family zinc finger 3 | Homo sapiens (human) | Potency | 13.3332 | 0.0007 | 14.5928 | 83.7951 | AID1259369; AID1259392 |
| progesterone receptor | Homo sapiens (human) | Potency | 33.4915 | 0.0004 | 17.9460 | 75.1148 | AID1346795 |
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 19.4971 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| retinoic acid nuclear receptor alpha variant 1 | Homo sapiens (human) | Potency | 8.9194 | 0.0030 | 41.6115 | 22,387.1992 | AID1159552; AID1159553 |
| estrogen-related nuclear receptor alpha | Homo sapiens (human) | Potency | 15.0594 | 0.0015 | 30.6073 | 15,848.9004 | AID1224841; AID1259401 |
| pregnane X nuclear receptor | Homo sapiens (human) | Potency | 26.6032 | 0.0054 | 28.0263 | 1,258.9301 | AID1346982 |
| G | Vesicular stomatitis virus | Potency | 27.5404 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 8.7090 | 0.0010 | 8.3798 | 61.1304 | AID1645840 |
| v-jun sarcoma virus 17 oncogene homolog (avian) | Homo sapiens (human) | Potency | 26.8325 | 0.0578 | 21.1097 | 61.2679 | AID1159526 |
| heat shock protein beta-1 | Homo sapiens (human) | Potency | 33.4889 | 0.0420 | 27.3789 | 61.6448 | AID743210 |
| nuclear factor erythroid 2-related factor 2 isoform 1 | Homo sapiens (human) | Potency | 23.7083 | 0.0006 | 27.2152 | 1,122.0200 | AID743202 |
| Interferon beta | Homo sapiens (human) | Potency | 27.5404 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 27.5404 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Spike glycoprotein | Severe acute respiratory syndrome-related coronavirus | Potency | 39.8107 | 0.0096 | 10.5250 | 35.4813 | AID1479145 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 27.5404 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 27.5404 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [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) |
|---|---|---|---|---|---|---|---|
| 5-hydroxytryptamine receptor 1A | Homo sapiens (human) | Ki | 0.1259 | 0.0001 | 0.5326 | 10.0000 | AID682996 |
| Alpha-2A adrenergic receptor | Homo sapiens (human) | Ki | 0.0044 | 0.0001 | 0.8074 | 10.0000 | AID648510 |
| Alpha-2B adrenergic receptor | Homo sapiens (human) | Ki | 0.0676 | 0.0002 | 0.7257 | 10.0000 | AID648511 |
| Alpha-2C adrenergic receptor | Homo sapiens (human) | Ki | 0.0692 | 0.0003 | 0.4834 | 10.0000 | AID648512 |
| Nischarin | Rattus norvegicus (Norway rat) | Ki | 0.0056 | 0.0008 | 0.1388 | 1.2589 | AID1306516 |
| [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) |
|---|---|---|---|---|---|---|---|
| Alpha-2A adrenergic receptor | Homo sapiens (human) | EC50 (µMol) | 0.0063 | 0.0008 | 0.3733 | 6.7100 | AID648513 |
| Alpha-2B adrenergic receptor | Homo sapiens (human) | EC50 (µMol) | 0.1259 | 0.0005 | 1.3644 | 6.7100 | AID648514 |
| Alpha-2C adrenergic receptor | Homo sapiens (human) | EC50 (µMol) | 0.0014 | 0.0005 | 0.5541 | 6.7100 | AID648515 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID648514 | Agonist activity at human adrenoceptor aplha 2B expressed in CHO cells assessed as rate of extracellular acidification by cytosensor microphysiometric analysis | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID648511 | Displacement of [3H]RS-79948-197 from human adrenoceptor aplha 2B expressed in CHO cells | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID648519 | Intrinsic activity at human adrenoceptor aplha 2C expressed in CHO cells by cytosensor microphysiometric analysis relative to (-)-noradrenaline | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID648518 | Intrinsic activity at human adrenoceptor aplha 2B expressed in CHO cells by cytosensor microphysiometric analysis relative to (-)-noradrenaline | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID1306516 | Displacement of [125I]PIC from Imidazoline-1 receptor in rat PC12 cell membrane incubated for 30 mins by gamma counting method | 2016 | Bioorganic & medicinal chemistry, 07-15, Volume: 24, Issue:14 | A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. |
| AID197169 | Hypertensive activity (increase in arterial pressure to 60 mmHg)) after i.v. administration to pithed rats. | 1984 | Journal of medicinal chemistry, Apr, Volume: 27, Issue:4 | Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists. |
| AID648515 | Agonist activity at human adrenoceptor aplha 2C expressed in CHO cells assessed as rate of extracellular acidification by cytosensor microphysiometric analysis | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID648513 | Agonist activity at human adrenoceptor aplha 2A expressed in CHO cells assessed as rate of extracellular acidification by cytosensor microphysiometric analysis | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID648517 | Intrinsic activity at human adrenoceptor aplha 2A expressed in CHO cells by cytosensor microphysiometric analysis relative to (-)-noradrenaline | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID648512 | Displacement of [3H]RS-79948-197 from human adrenoceptor aplha 2C expressed in CHO cells | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID36789 | Binding affinity against Alpha-2 adrenergic receptor is the ability to inhibit the specific [3H]clonidine binding (0.4 nM) to rat isolated brain membranes by 50% was reported; 2.5*10e-9 | 1984 | Journal of medicinal chemistry, Apr, Volume: 27, Issue:4 | Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists. |
| AID33252 | Peripheral hypertensive activity in pithed normotensive rats. | 1981 | Journal of medicinal chemistry, May, Volume: 24, Issue:5 | Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors. |
| AID23715 | Apparent partion coefficient of compound was evaluated in octanol/buffer at pH of 7.4 at 37 degree Centigrade | 1984 | Journal of medicinal chemistry, Apr, Volume: 27, Issue:4 | Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists. |
| AID36725 | Binding affinity against alpha-1 adrenergic receptor is the ability to inhibit the specific [3H]prazosin binding (0.2 nM) to rat isolated brain membranes by 50% was reported; 6.6*10e-7 | 1984 | Journal of medicinal chemistry, Apr, Volume: 27, Issue:4 | Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists. |
| AID182611 | Antisecretory activity determined after (sc) administration in rat using rat cholera toxin secretion assay | 1990 | Journal of medicinal chemistry, Feb, Volume: 33, Issue:2 | Potential antisecretory antidiarrheals. 2. Alpha 2-adrenergic 2-[(aryloxy)alkyl]imidazolines. |
| AID33250 | Central hypotensive activity in anesthetized normotensive rats. | 1981 | Journal of medicinal chemistry, May, Volume: 24, Issue:5 | Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors. |
| AID648510 | Displacement of [3H]RS-79948-197 from human adrenoceptor aplha 2A expressed in CHO cells | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID227718 | Binding energy by using the equation deltaG obsd = -RT ln KD | 1984 | Journal of medicinal chemistry, Dec, Volume: 27, Issue:12 | Functional group contributions to drug-receptor interactions. |
| AID682996 | Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HeLa cells after 30 mins | 2012 | ACS medicinal chemistry letters, Jul-12, Volume: 3, Issue:7 | Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine Dependence, Elicit an Antidepressant-like Effect. |
| AID197167 | Hypotensive activity (25% decrease in arterial pressure) after i.v. administration to anesthetized normotensive rats. | 1984 | Journal of medicinal chemistry, Apr, Volume: 27, Issue:4 | Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists. |
| AID23716 | Partition coefficient (logD7.4) | 1981 | Journal of medicinal chemistry, May, Volume: 24, Issue:5 | Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors. |
| AID1347103 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1745845 | Primary qHTS for Inhibitors of ATXN expression | |||
| AID1347107 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347097 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1508630 | Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay | 2021 | Cell reports, 04-27, Volume: 35, Issue:4 | A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome. |
| AID1347102 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347108 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347099 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID651635 | Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression | |||
| AID1347090 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347082 | qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal | 2020 | Antiviral research, 01, Volume: 173 | A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity. |
| AID1347425 | Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1) | 2019 | The Journal of biological chemistry, 11-15, Volume: 294, Issue:46 | Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens. |
| AID1347095 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347100 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347083 | qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen | 2020 | Antiviral research, 01, Volume: 173 | A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity. |
| AID1347093 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347407 | qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection | 2020 | ACS chemical biology, 07-17, Volume: 15, Issue:7 | High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle. |
| AID1347104 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347091 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347101 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347086 | qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal | 2020 | Antiviral research, 01, Volume: 173 | A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity. |
| AID1347105 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347089 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347096 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347106 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347154 | Primary screen GU AMC qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1347092 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347094 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1347424 | RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1) | 2019 | The Journal of biological chemistry, 11-15, Volume: 294, Issue:46 | Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens. |
| AID1347098 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 2018 | Oncotarget, Jan-12, Volume: 9, Issue:4 | Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing. |
| AID1159607 | Screen for inhibitors of RMI FANCM (MM2) intereaction | 2016 | Journal of biomolecular screening, Jul, Volume: 21, Issue:6 | A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway. |
| AID1346058 | Human alpha2B-adrenoceptor (Adrenoceptors) | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID1346159 | Human alpha2C-adrenoceptor (Adrenoceptors) | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| AID1346049 | Human alpha2A-adrenoceptor (Adrenoceptors) | 2012 | Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6 | Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations? |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 52 (35.86) | 18.7374 |
| 1990's | 16 (11.03) | 18.2507 |
| 2000's | 33 (22.76) | 29.6817 |
| 2010's | 35 (24.14) | 24.3611 |
| 2020's | 9 (6.21) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
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 very strong demand-to-supply ratio for research on this compound.
| This Compound (61.42) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 52 (32.91%) | 5.53% |
| Reviews | 23 (14.56%) | 6.00% |
| Case Studies | 3 (1.90%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 80 (50.63%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| A Study to Evaluate the Relative Bioavailability of a Test Formulation of Lofexidine Granules for Reconstitution and the Effect of Food on the Bioavailability of the Test Formulation in Healthy Adult Subjects [NCT04188730] | Phase 1 | 16 participants (Actual) | Interventional | 2021-02-16 | Completed | ||
| Evaluating a Mechanistically-Supported Pharmacotherapy to Treat Opioid Withdrawal [NCT05511909] | Phase 2 | 100 participants (Anticipated) | Interventional | 2022-12-15 | Recruiting | ||
| Lofexidine for Management of Opioid Withdrawal With XR-NTX Treatment [NCT04056182] | Phase 2 | 20 participants (Actual) | Interventional | 2019-09-01 | Completed | ||
| Phase 1, Double-Blind, Placebo-Controlled Assessment of Potential Interactions Between Intravenous Cocaine and Lofexidine [NCT01148992] | Phase 1 | 16 participants (Actual) | Interventional | 2010-08-31 | Terminated | ||
| Lofexidine Pharmacokinetics in the Presence of Paroxetine, a Strong CYP2D6 Inhibitor, in Healthy Volunteers [NCT02681198] | Phase 1 | 24 participants (Actual) | Interventional | 2016-01-31 | Completed | ||
| A Single-Center, Open-Label, Two-Period, Two-Treatment, Randomized Sequence Study to Determine the Mass Balance and Absolute Bioavailability of a Single Oral Dose of 14C-Labeled Lofexidine Compared to a Single Intravenous Dose of Lofexidine [NCT01310296] | Phase 1 | 12 participants (Actual) | Interventional | 2011-07-31 | Completed | ||
| A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Safety and Effectiveness of LUCEMYRA in the Treatment of Opioid Withdrawal During an Opioid Taper in Subjects With Chronic Non-Cancer Pain [NCT04070157] | Phase 2 | 60 participants (Anticipated) | Interventional | 2019-08-02 | Suspended(stopped due to COVID pandemic and enrollment issues necessitating an adjustment to the study design.) | ||
| Single-Dose Pharmacokinetics and Safety of Oral Lofexidine in Hepatically-Impaired Subjects [NCT02318836] | Phase 1 | 24 participants (Actual) | Interventional | 2014-06-30 | Completed | ||
| A Phase 1 Study to Evaluate the Relative Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction [NCT02801357] | Phase 1 | 10 participants (Actual) | Interventional | 2016-06-30 | Completed | ||
| A Randomized, Double-Blind, Placebo-Controlled Study of Lofexidine and Dronabinol for the Treatment of Marijuana Dependence [NCT01020019] | Phase 2/Phase 3 | 156 participants (Actual) | Interventional | 2010-01-31 | Completed | ||
| Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder [NCT05053503] | 168 participants (Anticipated) | Interventional | 2022-05-25 | Recruiting | |||
| Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal [NCT05995535] | Phase 2 | 150 participants (Anticipated) | Interventional | 2024-01-01 | Not yet recruiting | ||
| Assessing a Clinically-meaningful Opioid Withdrawal Phenotype [NCT05027919] | Phase 2 | 60 participants (Anticipated) | Interventional | 2022-02-01 | Recruiting | ||
| Lofexidine: Enhancing Naltrexone Treatment for Opiate Addiction [NCT00142909] | Phase 2 | 86 participants (Actual) | Interventional | 2005-02-28 | Completed | ||
| A Phase 2, Open-Label, Randomized, Controlled, Ascending Dose Cohort, Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids [NCT06047834] | Phase 2 | 24 participants (Anticipated) | Interventional | 2023-10-02 | Recruiting | ||
| Evaluating a Neuromodulator Medical Device (Bridge Device) for Opioid Use Disorder Treatment [NCT04325659] | Phase 2/Phase 3 | 75 participants (Anticipated) | Interventional | 2020-11-15 | Recruiting | ||
| A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Electrocardiographic Effects of Lofexidine When Administered Orally to Methadone Maintained Adult Subjects [NCT01650649] | Phase 1 | 27 participants (Actual) | Interventional | 2012-07-31 | Completed | ||
| Safety Evaluation of Lofexidine for Treatment of Opioid Withdrawal [NCT00000354] | Phase 1 | 0 participants | Interventional | 1996-07-31 | Completed | ||
| CSP #1024 - A Phase III, Randomized, Multi-Center, Double Blind, Placebo-Controlled Study of Safety and Efficacy of Lofexidine for Relief of Symptoms in Subjects Undergoing Inpatient Opiate Detoxification. [NCT00235729] | Phase 3 | 264 participants (Actual) | Interventional | 2006-06-30 | Completed | ||
| A Single-Dose, Open-Label, Randomized, Two-Way Crossover Food Effect Study of Lofexidine 400 μg (2 x 200 μg) Tablets [NCT01437306] | Phase 1 | 13 participants (Actual) | Interventional | 2011-10-31 | Completed | ||
| Evaluation of Lofexidine for Treatment of Opiate Withdrawal [NCT00000345] | Phase 1 | 0 participants | Interventional | 1996-04-30 | Completed | ||
| A Phase III Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal [NCT00032942] | Phase 3 | 66 participants | Interventional | 2001-04-30 | Completed | ||
| Naltrexone and Lofexidine in Detoxified Heroin Addicts [NCT00218530] | Phase 1 | 0 participants | Interventional | 2003-03-31 | Completed | ||
| Assessment of the Effect of Naltrexone on Lofexidine Single Dose Pharmacokinetics in Healthy Subjects [NCT02446002] | Phase 1 | 25 participants (Actual) | Interventional | 2015-05-31 | Completed | ||
| Phase 1B Study of Sublingual Dexmedetomidine, an Alpha 2 Adrenergic Agonist, for Treating Opioid Withdrawal [NCT05712707] | Phase 1/Phase 2 | 160 participants (Anticipated) | Interventional | 2023-02-28 | Recruiting | ||
| Impact of Lofexidine on Stress, Craving and Opioid Use [NCT03718065] | Phase 2 | 136 participants (Anticipated) | Interventional | 2019-06-26 | Recruiting | ||
| A Single-Center, Open-Label, Single-Period, Single-Treatment Study to Determine the Mass Balance of a Single Oral Dose of 14C Labeled Lofexidine [NCT01629446] | Phase 1 | 6 participants (Actual) | Interventional | 2012-05-31 | Completed | ||
| A Phase 3, Open-Label, Safety Study of Lofexidine [NCT02363998] | Phase 3 | 286 participants (Actual) | Interventional | 2015-02-28 | Completed | ||
| Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Dose-Response Study of Lofexidine for Treatment of Opioid Withdrawal (Days 1-7) Followed by Open-Label, Variable Dose Lofexidine Treatment (Days 8-14) [NCT01863186] | Phase 3 | 603 participants (Actual) | Interventional | 2013-06-30 | Completed | ||
| A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Electrocardiographic Effects of Lofexidine When Administered Orally to Buprenorphine-Maintained Adult Subjects [NCT01820442] | Phase 1 | 30 participants (Actual) | Interventional | 2013-03-31 | Completed | ||
| Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse [NCT00373503] | Phase 2 | 8 participants (Actual) | Interventional | 2005-08-31 | Completed | ||
| Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects [NCT02313103] | Phase 1 | 16 participants (Actual) | Interventional | 2014-11-30 | Completed | ||
| Safety Evaluation of Lofexidine for Treatment of Opioid Withdrawal [NCT00000358] | Phase 1 | 0 participants | Interventional | Completed | |||
| Lofexidine for Rapid Pre-Operative Opioid Tapering in Adults Undergoing Lumbar Spine Surgery [NCT04126083] | Phase 4 | 6 participants (Actual) | Interventional | 2019-09-01 | Completed | ||
| A Pilot, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Electrocardiographic Effects of Lofexidine When Administered Orally to Methadone Maintained Adult Subjects [NCT01558934] | Phase 1 | 6 participants (Actual) | Interventional | 2012-02-29 | Completed | ||
| A Comparative Study of the Efficacy of Venlafaxine and Naltrexone for Relapse Prevention in Patients With Opioid Use Disorder Attributed to Tramadol [NCT05569031] | Phase 4 | 52 participants (Actual) | Interventional | 2019-01-01 | Completed | ||
| Lofexidine Combined With Buprenorphine for Reducing Symptoms of Post-Traumatic Stress Disorder (PTSD) and Opioid Use Relapse in Veterans [NCT04360681] | Phase 2 | 120 participants (Anticipated) | Interventional | 2021-03-09 | Recruiting | ||
| Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM): Can it Increase the Success of Transition to Naltrexone? [NCT04218240] | Phase 2 | 90 participants (Actual) | Interventional | 2020-12-20 | Completed | ||
| A Double-blind Randomised Controlled Clinical Trial of Lofexidine Versus Diazepam in the Management of the Opioid Withdrawal Syndrome During Inpatient Detoxification in Singapore [NCT01675648] | Phase 4 | 112 participants (Actual) | Interventional | 2012-08-31 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||