Potentiating effects of L-type Ca(2+) channel blockers on pentobarbital-induced hypnosis are influenced by serotonergic system.
In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca(2+) antagonists, the effects of three structurally diverse types of Ca(2+) antagonists combined or not with 5-HT on pentobarbital-induced hypnosis in mice were investigated. The results showed that dihydropyridine derivative nifedipine (10.0 and 20.0 mg/kg, p.o.) and other types of Ca(2+) antagonist, verapamil (5.0 and 10.0 mg/kg, p.o.) and diltiazem (2.5, 5.0 and 10.0 mg/kg, p.o.) increased both the sleeping time in hypnotic dosage of pentobarbital (45 mg/kg, i.p.) treated mice and the rate of sleep onset in the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.) treated mice in a dose-dependent manner, respectively, and these effects were significantly augmented by 5-hydroxytryptophan (5-HTP), the immediate precursor of 5-hydroxytryptamine (5-HT). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping time and nifedipine (10.0 mg/kg, p.o.), verapamil (5.0 mg/kg, p.o.) and diltiazem (2.5 mg/kg, p.o.) abolished this effect. From these results, it should be presumed that the augmentative effect of L-type Ca(2+) channel blockers on pentobarbital-induced sleep may be influenced by serotonergic system.
Zhao
X
X
Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing, China.
Cui
X-Y
XY
Chu
Q-P
QP
Chen
B-Q
BQ
Wang
X-M
XM
Lin
Z-B
ZB
Li
X-J
XJ
Ku
B-S
BS
Zhang
Y-H
YH
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D010134:Fenclonine / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009543:Nifedipine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006993:Hypnotics and Sedatives; D012702:Serotonin Antagonists; D012701:Serotonin; D006916:5-Hydroxytryptophan; D014700:Verapamil; D004110:Diltiazem; D010424:Pentobarbital; D009543:Nifedipine; D010134:Fenclonine