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Potentiating effects of L-type Ca2+ channel blockers on pentobarbital-induced hypnosis are influenced by serotonergic system

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In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca2+ antagonists, the effects of three structurally diverse types of Ca2+ 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 Ca2+ 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 Ca2+ channel blockers on pentobarbital-induced sleep may be influenced by serotonergic system.

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Authors and Affiliations

  1. Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing, China

    X. Zhao, X.-Y. Cui, Q.-P. Chu, B.-Q. Chen, Z.-B. Lin, X.-J. Li, B.-S. Ku & Y.-H. Zhang

  2. Department of Physiology, Capital University of Medical Science, Beijing, China

    X.-M. Wang

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Zhao, X., Cui, XY., Chu, QP. et al. Potentiating effects of L-type Ca2+ channel blockers on pentobarbital-induced hypnosis are influenced by serotonergic system. J Neural Transm 113, 1395–1402 (2006). https://doi.org/10.1007/s00702-005-0422-1

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