Influence of some agents that affect 5-hydroxytryptamine metabolism and receptors on nitrazepam-induced sleep in mice.
The effects of 5-hydroxytryptophan (5-HTP), citalopram, p-chlorophenylalanine (PCPA), cyproheptadine, lysergic acid diethylamide (LSD-25), metitepine and NSD 1034 on nitrazepam-induced sleep were investigated in mice. Nitrazepam (1.6-25.6 mg kg-1, i.p.) induced a dose-dependent sedative-hypnotic effect. 5-HTP (8-128 mg kg-1 i.m.) did not induce behavioural sleep but sedated mice and significantly potentiated nitrazepam-induced sleep. Similarly, 5-HTP (4-32 mg kg-1, i.m.) increased pentobarbitone sleeping time. Citalopram (2.5-10 mg kg-1, i.p.) significantly potentiated nitrazepam sleep. PCPA (300-400 mg kg-1, i.p.) completely abolished nitrazepam sleep; 5-HTP (32 mg kg-1, i.m.) reversed this effect. NSD 1034 (75-150 mg kg-1, i.p.) antagonized the potentiating effect of 5-HTP (32 mg kg-1, i.m.) on nitrazepam sleep. Cyproheptadine (5-10 mg kg-1, i.p.) and LSD-25 (2.5-10 micrograms kg-1, i.p.) partially antagonized nitrazepam sleep. Similarly, 5-HTP-induced potentiation of nitrazepam sleep was antagonized by cyproheptadine and LSD-25. Metitepine (4-8 mg kg-1, i.p.) induced behavioural sleep and significantly potentiated nitrazepam sleep. Ro15-1788 (10 mg kg-1, i.p.) effectively antagonized nitrazepam-induced sleep. These results indicate that enhancement of central 5-HT neurotransmission may underlie nitrazepam-induced sleep in mice.
Wambebe
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D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D015283:Citalopram; D003533:Cyproheptadine / Q000494:pharmacology; D004357:Drug Synergism; D010134:Fenclonine / Q000494:pharmacology; D005442:Flumazenil; D006834:Hydrazines / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D051379:Mice; D009567:Nitrazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects*
D001570:Benzodiazepinones; D006834:Hydrazines; D011437:Propylamines; D011985:Receptors, Serotonin; D015283:Citalopram; D003533:Cyproheptadine; D012701:Serotonin; D005442:Flumazenil; C020173:NSD 1034; D008719:Methiothepin; D008238:Lysergic Acid Diethylamide; D009567:Nitrazepam; D006916:5-Hydroxytryptophan; D010134:Fenclonine