Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators

Frontiers in Neuroscience

Volumn , Issue 7 DEC, 2013, Pages

  Ramirez, Andres D ^a   Gotter, Anthony L ^a   Fox, Steven V ^a   Tannenbaum, Pamela L ^a   Yao, Lihang ^a   Tye, Spencer J ^a   McDonald, Terrence ^a   Brunner, Joseph ^a   Garson, Susan L ^a   Reiss, Duane R ^a   Kuduk, Scott D ^a   Coleman, Paul J ^a   Uslaner, Jason M ^a   Hodgson, Robert ^a   Browne, Susan E ^a   Renger, John J ^a   Winrow, Christopher J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Dual orexin receptor antagonist; Ethanol; GABA; Insomnia; Locomotor performance; Orexin; Rats; Sleep

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; ALCOHOL; ALMOREXANT; DIAZEPAM; DUAL OREXIN RECEPTOR ANTAGONIST; DUAL OREXIN RECEPTOR ANTAGONIST 12; ESZOPICLONE; UNCLASSIFIED DRUG; ZOLPIDEM;

ALCOHOL METABOLISM; ANIMAL EXPERIMENT; ARTICLE; CHEMICAL STRUCTURE; CLINICAL EVALUATION; CONTROLLED STUDY; ELECTROENCEPHALOGRAM; MALE; MOTOR PERFORMANCE; NONHUMAN; RAT; ROTAROD TEST; SLEEP ARCHITECTURE; SLEEP PATTERN; WALKING;

EID: 84898037718     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2013.00254     Document Type: Article

References (67)

1. Allain, H., Bentue-Ferrer, D., Polard, E., Akwa, Y., and Patat, A. (2005). Postural instability and consequent falls and hip fractures associated with use of hypnotics in the elderly: a comparative review. Drugs Aging 22, 749-765. doi: 10.2165/00002512-200522090-00004
2. Arbilla, S., Depoortere, H., George, P., and Langer, S. Z. (1985). Pharmacological profile of the imidazopyridine zolpidem at benzodiazepine receptors and electrocorticogram in rats. Naunyn Schmiedebergs. Arch. Pharmacol. 330, 248-251. doi: 10.1007/BF00572441
3. Barbone, F., McMahon, A. D., Davey, P. G., Morris, A. D., Reid, I. C., McDevitt, D. G., et al. (1998). Association of road-traffic accidents with benzodiazepine use. Lancet 352, 1331-1336. doi: 10.1016/S0140-6736(98)04087-2
4. Barker, M. J., Greenwood, K. M., Jackson, M., and Crowe, S. F. (2004). Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs 18, 37-48. doi: 10.2165/00023210-200418010-00004
5. Bettica, P., Nucci, G., Pyke, C., Squassante, L., Zamuner, S., Ratti, E., et al. (2012a). Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. J. Psychopharmacol. 26, 1058-1070. doi: 10.1177/0269881111408954
6. Bettica, P., Squassante, L., Zamuner, S., Nucci, G., Danker-Hopfe, H., and Ratti, E. (2012b). The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep 35, 1097-1104. doi: 10.5665/sleep.1996
7. Bettica, P., Squassante, L., Groeger, J. A., Gennery, B., Winsky-Sommerer, R., and Dijk, D. J. (2012c). 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. doi: 10.1038/npp.2011.310
8. Bianchi, M. T. (2010). Context dependent benzodiazepine modulation of GABA(A) receptor opening frequency. Curr. Neuropharmacol. 8, 10-17. doi: 10.2174/157015910790909467
9. Brisbare-Roch, C., Dingemanse, J., Koberstein, R., Hoever, P., Aissaoui, H., Flores, S., et al. (2007). Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat. Med. 13, 150-155. doi: 10.1038/nm1544
10. Brunner, D. P., Dijk, D. J., Munch, M., and Borbely, A. A. (1991). Effect of zolpidem on sleep and sleep EEG spectra in healthy young men. Psychopharmacology (Berl.) 104, 1-5. doi: 10.1007/BF02244546
11. Cagetti, E., Liang, J., Spigelman, I., and Olsen, R. W. (2003). Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol. Pharmacol. 63, 53-64. doi: 10.1124/mol.63.1.53
12. Chang, C. M., Wu, E. C., Chen, C. Y., Wu, K. Y., Liang, H. Y., Chau, Y. L., et al. (2013). Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study. Br. J. Clin. Pharmacol. 75, 1125-1133. doi: 10.1111/j.1365-2125.2012.04410.x
13. Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., et al. (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98, 437-451. doi: 10.1016/S0092-8674(00)81973-X
14. Christophersen, A. S., and Morland, J. (2008). Frequent detection of benzodiazepines in drugged drivers in Norway. Traffic Inj. Prev. 9, 98-104. doi: 10.1080/15389580701869190
15. Devaud, L. L., Purdy, R. H., Finn, D. A., and Morrow, A. L. (1996). Sensitization of gamma-aminobutyric acidA receptors to neuroactive steroids in rats during ethanol withdrawal. J. Pharmacol. Exp. Ther. 278, 510-517.
16. Ensrud, K. E., Blackwell, T. L., Mangione, C. M., Bowman, P. J., Whooley, M. A., Bauer, D. C., et al. (2002). Central nervous system-active medications and risk for falls in older women. J. Am. Geriatr. Soc. 50, 1629-1637. doi: 10.1046/j.1532-5415.2002.50453.x
17. Fox, S. V., Gotter, A. L., Tye, S. J., Garson, S. L., Savitz, A. T., Uslaner, J. M., et al. (2013). Quantitative electroencephalography within sleep/wake states differentiates GABA-A modulators eszopiclone and zolpidem from dual orexin receptor antagonists in rats. Neuropsychopharmacology 38, 2401-2408. doi: 10.1038/npp.2013.139
18. Gerashchenko, D., Blanco-Centurion, C., Greco, M. A., and Shiromani, P. J. (2003). Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats. Neuroscience 116, 223-235. doi: 10.1016/S0306-4522(02)00575-4
19. Gotter, A. L., Webber, A. L., Coleman, P. J., Renger, J. J., and Winrow, C. J. (2012). International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin receptor function, nomenclature and pharmacology. Pharmacol. Rev. 64, 389-420. doi: 10.1124/pr.111.005546
20. Gotter, A. L., Winrow, C. J., Brunner, J., Garson, S. L., Fox, S. V., Binns, J., et al. (2013). The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold. BMC Neurosci. 14:90. doi: 10.1186/1471-2202-14-90
21. Graham, D., Faure, C., Besnard, F., and Langer, S. Z. (1996). Pharmacological profile of benzodiazepine site ligands with recombinant GABAA receptor subtypes. Eur. Neuropsychopharmacol. 6, 119-125. doi: 10.1016/0924-977X(95)00072-W
22. Hanchar, H. J., Dodson, P. D., Olsen, R. W., Otis, T. S., and Wallner, M. (2005). Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity. Nat. Neurosci. 8, 339-345. doi: 10.1038/nn1398
23. Herring, W. J., Connor, K., Ivgy-May, N., Snavely, D., Snyder, E., Liu, K., et al. (2012a). "Efficacy and safety of suvorexant, a dual orexin receptor antagonist, in patients with primary insomnia: results from two pivotal trials," in 26th Annual Meeting of the Associated Professional Sleep Societies, (Boston, MA).
24. Herring, W. J., Snyder, E., Budd, K., Hutzelmann, J., Snavely, D., Liu, K., et al. (2012b). Orexin receptor antagonism for treatment of insomnia: A randomized clinical trial of suvorexant. Neurology 79, 2265-2274. doi: 10.1212/WNL.0b013e31827688ee
25. Hindmarch, I., Legangneux, E., Stanley, N., Emegbo, S., and Dawson, J. (2006). A double-blind, placebo-controlled investigation of the residual psychomotor and cognitive effects of zolpidem-MR in healthy elderly volunteers. Br. J. Clin. Pharmacol. 62, 538-545. doi: 10.1111/j.1365-2125.2006.02705.x
26. Hoch, M., Hay, J. L., Hoever, P., de Kam, M. L., Te Beek, E. T., van Gerven, J. M., et al. (2013). Dual orexin receptor antagonism by almorexant does not potentiate impairing effects of alcohol in humans. Eur. Neuropsychopharmacol. 23, 107-117. doi: 10.1016/j.euroneuro.2012.04.012
27. Hoever, P., Dorffner, G., Benes, H., Penzel, T., Danker-Hopfe, H., Barbanoj, M. J., et al. (2012). Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial. Clin. Pharmacol. Ther. 91, 975-985. doi: 10.1038/clpt.2011.370
28. Ilomaki, J., Korhonen, M. J., Enlund, H., Hartzema, A. G., and Kauhanen, J. (2008). Risk drinking behavior among psychotropic drug users in an aging Finnish population: the FinDrink study. Alcohol 42, 261-267. doi: 10.1016/j.alcohol.2008.02.002
29. Johnson, E. O., Roehrs, T., Roth, T., and Breslau, N. (1998). Epidemiology of alcohol and medication as aids to sleep in early adulthood. Sleep 21, 178-186.
30. Kiyashchenko, L. I., Mileykovskiy, B. Y., Maidment, N., Lam, H. A., Wu, M. F., John, J., et al. (2002). Release of hypocretin (orexin) during waking and sleep states. J. Neurosci. 22, 5282-5286. Available online at: http://www.jneurosci.org/content/22/13/5282.long
31. Kurzthaler, I., Wambacher, M., Golser, K., Sperner, G., Sperner-Unterweger, B., Haidekker, A., et al. (2005). Alcohol and/or benzodiazepine use: different accidents-different impacts? Hum. Psychopharmacol. 20, 583-589. doi: 10.1002/hup.736
32. Legrand, S. A., Gjerde, H., Isalberti, C., Van der Linden, T., Lillsunde, P., Dias, M. J., et al. (2013). Prevalence of alcohol, illicit drugs and psychoactive medicines in killed drivers in four European countries. Int. J. Inj. Contr. Saf. Promot. doi: 10.1080/17457300.2012.748809. [Epub ahead of print].
33. Leipzig, R. M., Cumming, R. G., and Tinetti, M. E. (1999). Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J. Am. Geriatr. Soc. 47, 30-39.
34. Lin, J. S., Sakai, K., and Jouvet, M. (1988). Evidence for histaminergic arousal mechanisms in the hypothalamus of cat. Neuropharmacology 27, 111-122. doi: 10.1016/0028-3908(88)90159-1
35. Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X. Y., et al. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98, 365-376. doi: 10.1016/S0092-8674(00)81965-0
36. Lovinger, D. M., and Roberto, M. (2013). Synaptic effects induced by alcohol. Curr. Top. Behav. Neurosci. 13, 31-86. doi: 10.1007/7854_2011_143
37. Marcus, J. N., Aschkenasi, C. J., Lee, C. E., Chemelli, R. M., Saper, C. B., Yanagisawa, M., et al. (2001). Differential expression of orexin receptors 1 and 2 in the rat brain. J. Comp. Neurol. 435, 6-25. doi: 10.1002/cne.1190
38. Maxwell, H. G., Dubois, S., Weaver, B., and Bedard, M. (2010). The additive effects of alcohol and benzodiazepines on driving. Can. J. Public Health 101, 353-357. Available online at: http://journal.cpha.ca/index.php/cjph/article/view/1975
39. McKernan, R. M., Rosahl, T. W., Reynolds, D. S., Sur, C., Wafford, K. A., Atack, J. R., et al. (2000). Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat. Neurosci. 3, 587-592. doi: 10.1038/75761
40. Mohler, H. (2006). GABA(A) receptor diversity and pharmacology. Cell Tissue Res. 326, 505-516. doi: 10.1007/s00441-006-0284-3
41. Nishino, S., Ripley, B., Overeem, S., Lammers, G. J., and Mignot, E. (2000). Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355, 39-40. doi: 10.1016/S0140-6736(99)05582-8
42. Ohno, K., and Sakurai, T. (2008). Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front. Neuroendocrinol. 29, 70-87. doi: 10.1016/j.yfrne.2007.08.001
43. Otmani, S., Demazieres, A., Staner, C., Jacob, N., Nir, T., Zisapel, N., et al. (2008). Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum. Psychopharmacol. 23, 693-705. doi: 10.1002/hup.980
44. Peyron, C., Tighe, D. K., van den Pol, A. N., de Lecea, L., Heller, H. C., Sutcliffe, J. G., et al. (1998). Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18, 9996-10015.
45. Ray, W. A., Thapa, P. B., and Gideon, P. (2000). Benzodiazepines and the risk of falls in nursing home residents. J. Am. Geriatr. Soc. 48, 682-685. Available onine at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291532-5415/issues
46. Renger, J. J., Dunn, S. L., Motzel, S. L., Johnson, C., and Koblan, K. S. (2004). Sub-chronic administration of zolpidem affects modifications to rat sleep architecture. Brain Res. 1010, 45-54. doi: 10.1016/j.brainres.2004.02.067
47. Ricci, G., Majori, S., Mantovani, W., Zappaterra, A., Rocca, G., and Buonocore, F. (2008). Prevalence of alcohol and drugs in urine of patients involved in road accidents. J. Prev. Med. Hyg. 49, 89-95. Available online at: http://www.jpmh.org/issues.htm
48. Rudolph, U., Crestani, F., Benke, D., Brunig, I., Benson, J. A., Fritschy, J. M., et al. (1999). Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. Nature 401, 796-800. doi: 10.1038/44579
49. Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., et al. (1998). Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573-585. doi: 10.1016/S0092-8674(00)80949-6
50. Saper, C. B., Scammell, T. E., and Lu, J. (2005). Hypothalamic regulation of sleep and circadian rhythms. Nature 437, 1257-1263. doi: 10.1038/nature04284
51. Scammell, T. E., and Winrow, C. J. (2011). Orexin receptors: pharmacology and therapeutic opportunities. Annu. Rev. Pharmacol. Toxicol. 51, 243-266. doi: 10.1146/annurev-pharmtox-010510-100528
52. Sieghart, W., and Sperk, G. (2002). Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr. Top. Med. Chem. 2, 795-816. doi: 10.2174/1568026023393507
53. Stein, M. D., and Friedmann, P. D. (2005). Disturbed sleep and its relationship to alcohol use. Subst. Abus. 26, 1-13. doi: 10.1300/J465v26n01_01
54. Steiner, M. A., Lecourt, H., Strasser, D. S., Brisbare-Roch, C., and Jenck, F. (2011). 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 36, 848-856. doi: 10.1038/npp.2010.224
55. Tanaka, E. (2002). Toxicological interactions between alcohol and benzodiazepines. J. Toxicol. Clin. Toxicol. 40, 69-75. doi: 10.1081/CLT-120002887
56. Thompson, R. H., Canteras, N. S., and Swanson, L. W. (1996). Organization of projections from the dorsomedial nucleus of the hypothalamus: a PHA-L study in the rat. J. Comp. Neurol. 376, 143-173. doi: 10.1002/(SICI)1096-9861(19961202)376:1<143::AID-CNE9>3.0.CO;2-3
57. Titler, M. G., Shever, L. L., Kanak, M. F., Picone, D. M., and Qin, R. (2011). Factors associated with falls during hospitalization in an older adult population. Res. Theory Nurs. Pract. 25, 127-148. doi: 10.1891/1541-6577.25.2.127
58. Trivedi, P., Yu, H., MacNeil, D. J., Van der Ploeg, L. H. T., and Guan, X. M. (1998). Distribution of orexin receptor mRNA in the rat brain. FEBS Lett. 438, 71-75. doi: 10.1016/S0014-5793(98)01266-6
59. Tsunematsu, T., Kilduff, T. S., Boyden, E. S., Takahashi, S., Tominaga, M., and Yamanaka, A. (2011). Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J. Neurosci. 31, 10529-10539. doi: 10.1523/JNEUROSCI.0784-11.2011
60. Vermeeren, A., and Coenen, A. M. (2011). Effects of the use of hypnotics on cognition. Prog. Brain Res. 190, 89-103. doi: 10.1016/B978-0-444-53817-8.00005-0
61. Vermeeren, A., Vuurman, E., Bautmans, A., Li, X., Vets, E., Lewis, N., et al. (2012). Suvorexant, a dual orexin receptor antagonist, does not impair next day driving performance in healthy elderly subjects. J. Sleep Sleep Disord. Res. 35, A226, 0670 (Abstract).
62. Winrow, C. J., Gotter, A. L., Cox, C. D., Doran, S. M., Tannenbaum, P. L., Breslin, M. J., et al. (2011). Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist. J. Neurogenet. 25, 52-61. doi: 10.3109/01677063.2011.566953
63. Winrow, C. J., Gotter, A. L., Cox, C. D., Tannenbaum, P. L., Garson, S. L., Doran, S. M., et al. (2012). Pharmacological characterization of MK-6096-a dual orexin receptor antagonist for insomnia. Neuropharmacology 62, 978-987. doi: 10.1016/j.neuropharm.2011.10.003
64. Winrow, C. J., and Renger, J. J. (2013). Discovery and development of orexin receptor antagonists as therapeutics for insomnia. Br. J. Pharmacol. doi: 10.1111/bph.12261. [Epub ahead of print].
65. Woratanarat, P., Ingsathit, A., Suriyawongpaisal, P., Rattanasiri, S., Chatchaipun, P., Wattayakorn, K., et al. (2009). Alcohol, illicit and non-illicit psychoactive drug use and road traffic injury in Thailand: a case-control study. Accid. Anal. Prev. 41, 651-657. doi: 10.1016/j.aap.2009.03.002
66. Yoshida, K., McCormack, S., Espana, R. A., Crocker, A., and Scammell, T. E. (2006). Afferents to the orexin neurons of the rat brain. J. Compar. Neurol. 494, 845-861. doi: 10.1002/cne.20859
67. Yoshida, Y., Fujiki, N., Nakajima, T., Ripley, B., Matsumura, H., Yoneda, H., et al. (2001). Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur. J. Neurosci. 14, 1075-1081. doi: 10.1046/j.0953-816x.2001.01725.x