Dual orexin receptor antagonism by almorexant does not potentiate impairing effects of alcohol in humans

European Neuropsychopharmacology

Volumn 23, Issue 2, 2013, Pages 107-117

  Hoch, Matthias ^a   Hay, Justin L ^b   Hoever, Petra ^a   de Kam, Marieke L ^b   te Beek, Erik T ^b   van Gerven, Joop M A ^b   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

^b CENTRE FOR HUMAN DRUG RESEARCH   (Netherlands)

Author keywords

Alcohol interaction; Almorexant; Ethanol; Orexin; Pharmacodynamics; Pharmacokinetics

Indexed keywords

ALCOHOL; ALMOREXANT; PLACEBO;

ADULT; AGED; ALCOHOL INTOXICATION; ALERTNESS; ARTICLE; BODY EQUILIBRIUM; COGNITION; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG INDUCED HEADACHE; EYE MOVEMENT; FATIGUE; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; MEMORY; NAUSEA; NORMAL HUMAN; PRIORITY JOURNAL; PSYCHOMOTOR PERFORMANCE; SOMNOLENCE; VISUAL ANALOG SCALE;

ACETAMIDES; ADOLESCENT; ADULT; AFFECT; ALCOHOLIC INTOXICATION; AROUSAL; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; DRUG SYNERGISM; ETHANOL; EYE MOVEMENTS; FEMALE; HUMANS; ISOQUINOLINES; MALE; MEMORY; MIDDLE AGED; OREXIN RECEPTORS; POSTURE; PSYCHOMOTOR PERFORMANCE;

EID: 84873524976     PISSN: 0924977X     EISSN: 18737862     Source Type: Journal    
DOI: 10.1016/j.euroneuro.2012.04.012     Document Type: Article

References (38)

1. Bettica P., Nucci G., Pyke C., Squassante L., Zamuner S., Ratti E., Gomeni R., Alexander R. Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. J. Psychopharmacol. 2011, (e-pub ahead).
2. Bettica, P., Squassante, L., Groeger, J.A., Gennery, B., Winsky-Sommerer, R., Dijk, D.J., 2012. Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia. Neuropsychopharmacology 37, 1224-1233.
3. Bond A., Lader M. The use of analogue scales in rating subjective feelings. Br. J. Med. Psychol. 1974, 47:211-218.
4. Brevig H.N., Watson C.J., Lydic R., Baghdoyan H.A. Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness. Sleep 2010, 33:1285-1293.
5. Brisbare-Roch C., Dingemanse J., Koberstein R., Hoever P., Aissaoui H., Flores S., Mueller C., Nayler O., van Gerven J., de Haas S.L., Hess P., Qiu C., Buchmann S., Scherz M., Weller T., Fischli W., Clozel M., Jenck F. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat. Med. 2007, 13:150-155.
6. Dingemanse J., Dorffner G., Hajak G., Benes H., Danker-Hopfe H., Polo O., Saletu B., Barbanoj M., Pillar G., Penzel T., Chiossi E., Hoever P. Proof-of-concept study in primary insomnia patients with ACT-078573, a dual orexin receptor antagonist. Sleep Biol. Rhythms 2007, 5(Suppl. s1):A194.
7. Edwards D.J., Babiak L.M., Beckman H.B. The effect of a single oral dose of ethanol on hepatic blood flow in man. Eur. J. Clin. Pharmacol. 1987, 32:481-484.
8. Harris R.A., Trudell J.R., Mihic S.J. Ethanol's molecular targets. Sci. Signal 2008, 1:re7.
9. Hesse L.M., von Moltke L.L., Greenblatt D.J. Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs 2003, 17:513-532.
10. Hoch M., Hoever P., Haschke M., Krahenbühl S., Dingemanse J. Food effect and biocomparison of two formulations of the dual orexin receptor antagonist almorexant in healthy male subjects. J. Clin. Pharmacol. 2011, 51:1116-1121.
11. Hoever P., de Haas S., Winkler J., Schoemaker R.C., Chiossi E., van Gerven J., Dingemanse J. Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant. Clin. Pharmacol. Ther. 2010, 87:593-600.
12. Hollister L.E. Interactions between alcohol and benzodiazepines. Recent Dev. Alcohol 1990, 8:233-239.
13. Kuitunen T., Mattila M.J., Seppala T. Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam and alcohol. Int. Clin. Psychopharmacol. 1990, 5(Suppl. 2):115-130.
14. Kurzthaler I., Wambacher M., Golser K., Sperner G., Sperner-Unterweger B., Haidekker A., Pavlic M., Kemmler G., Fleischhacker W.W. Alcohol and benzodiazepines in falls: an epidemiological view. Drug Alcohol Depend. 2005, 79:225-230.
15. Kurzthaler I., Wambacher M., Golser K., Sperner G., Sperner-Unterweger B., Haidekker A., Pavlic M., Kemmler G., Fleischhacker W.W. Alcohol and/or benzodiazepine use: different accidents-different impacts?. Hum. Psychopharmacol. 2005, 20:583-589.
16. Matsuki T., Nomiyama M., Takahira H., Hirashima N., Kunita S., Takahashi S., Yagami K., Kilduff T.S., Bettler B., Yanagisawa M., Sakurai T. Selective loss of GABA(B) receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc. Natl. Acad. Sci. U S A 2009, 106:4459-4464.
17. Mignot E., Nishino S. Emerging therapies in narcolepsy-cataplexy. Sleep 2005, 28:754-763.
18. Mody I., Glykys J., Wei W. A new meaning for "Gin & Tonic": tonic inhibition as the target for ethanol action in the brain. Alcohol 2007, 41:145-153.
19. O'Connor S., Morzorati S., Christian J., Li T.K. Clamping breath alcohol concentration reduces experimental variance: application to the study of acute tolerance to alcohol and alcohol elimination rate. Alcohol Clin. Exp. Res. 1998, 22:202-210.
20. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat. Rev. Neurosci. 2007, 8:171-181.
21. Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M., Tanaka H., Williams S.C., Richardson J.A., Kozlowski G.P., Wilson S., Arch J.R., Buckingham R.E., Haynes A.C., Carr S.A., Annan R.S., McNulty D.E., Liu W.S., Terrett J.A., Elshourbagy N.A., Bergsma D.J., Yanagisawa M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998, 92:573-585.
22. Stein M.D., Friedmann P.D. Disturbed sleep and its relationship to alcohol use. Subst. Abus. 2005, 26:1-13.
23. Steiner M.A., Lecourt H., Strasser D.S., Brisbare-Roch C., Jenck F. Differential effects of the dual orexin receptor antagonist almorexant and the GABA(A)-alpha1 receptor modulator zolpidem, alone or combined with ethanol, on motor performance in the rat. Neuropsychopharmacology 2011, 36:848-856.
24. Sullivan S.S., Guilleminault C. Emerging drugs for insomnia: new frontiers for old and novel targets. Expert Opin. Emerg. Drugs 2009, 14:411-422.
25. Szymusiak R., McGinty D. Hypothalamic regulation of sleep and arousal. Ann. N. Y. Acad. Sci. 2008, 1129:275-286.
26. Tsujino N., Sakurai T. Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol. Rev. 2009, 61:162-176.
27. van Steveninck A.L., Gieschke R., Schoemaker H.C., Pieters M.S., Kroon J.M., Breimer D.D., Cohen A.F. Pharmacodynamic interactions of diazepam and intravenous alcohol at pseudo steady state. Psychopharmacology (Berlin) 1993, 110:471-478.
28. van Steveninck A.L., Gieschke R., Schoemaker R.C., Roncari G., Tuk B., Pieters M.S., Breimer D.D., Cohen A.F. Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol. Br. J. Clin. Pharmacol. 1996, 41:565-573.
29. van Steveninck A.L., Schoemaker H.C., Pieters M.S., Kroon R., Breimer D.D., Cohen A.F. A comparison of the sensitivities of adaptive tracking, eye movement analysis and visual analog lines to the effects of incremental doses of temazepam in healthy volunteers. Clin. Pharmacol. Ther. 1991, 50:172-180.
30. van Steveninck A.L., van Berckel B.N., Schoemaker R.C., Breimer D.D., van Gerven J.M., Cohen A.F. The sensitivity of pharmacodynamic tests for the central nervous system effects of drugs on the effects of sleep deprivation. J. Psychopharmacol. 1999, 13:10-17.
31. Watson P.E., Watson I.D., Batt R.D. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am. J. Clin. Nutr. 1980, 33:27-39.
32. Wilkinson C.J. The acute effects of zolpidem, administered alone and with alcohol, on cognitive and psychomotor function. J. Clin. Psychiatry 1995, 56:309-318.
33. Winrow C.J., Gotter A.L., Cox C.D., Doran S.M., Tannenbaum P.L., Breslin M.J., Garson S.L., Fox S.V., Harrell C.M., Stevens J., Reiss D.R., Cui D., Coleman P.J., Renger J.J. Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist. J. Neurogenet. 2011, 25:52-61.
34. Winrow C.J., Gotter A.L., Cox C.D., Tannenbaum P.L., Garson S.L., Doran S.M., Breslin M.J., Schreier J.D., Fox S.V., Harrell C.M., Stevens J., Reiss D.R., Cui D., Coleman P.J., Renger J.J. Pharmacological characterization of MK-6096-a dual orexin receptor antagonist for insomnia. Neuropharmacology 2011, (e-pub ahead).
35. Xie X., Crowder T.L., Yamanaka A., Morairty S.R., Lewinter R.D., Sakurai T., Kilduff T.S. GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus. J. Physiol. 2006, 574:399-414.
36. Yamanaka A., Muraki Y., Tsujino N., Goto K., Sakurai T. Regulation of orexin neurons by the monoaminergic and cholinergic systems. Biochem. Biophys. Res. Commun. 2003, 303:120-129.
37. Zoethout R.W., Schoemaker R.C., Zuurman L., van Pelt H., Dahan A., Cohen A.F., van Gerven J.M. Central nervous system effects of alcohol at a pseudo-steady-state concentration using alcohol clamping in healthy volunteers. Br. J. Clin. Pharmacol. 2009, 68:524-534.
38. Zoethout R.W., van Gerven J.M., Dumont G.J., Paltansing S., van Burgel N.D., van der Linden M., Dahan A., Cohen A.F., Schoemaker R.C. A comparative study of two methods for attaining constant alcohol levels. Br. J. Clin. Pharmacol. 2008, 66:674-681.