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Interference of antimycotics and other drugs with methohexital hypnosis in rats
Author(s) -
Awouters Frans,
Niemegeers Carlos J. E.,
Janssen Paul A. J.
Publication year - 1989
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430160110
Subject(s) - methohexital , phenobarbital , hypnosis , meprobamate , pharmacology , hypnotic , chemistry , anesthesia , medicine , alternative medicine , pathology , propofol
Compounds of various pharmacological and chemical classes were studied for their interaction with methohexital hypnosis. Rats were treated daily for 5 days with an oral dose of a test compound or solvent. On days 1, 5, and 8 methohexital was injected intraperitoneally and the duration of hypnosis was measured. Three types of interaction with methohexital hypnosis were observed. Acute prolongation of hypnosis on day 1 was the most marked effect of fluconazole (median effective dose, ED 50 : 8.66 mg/kg), but this occurred also with phenobarbital (ED 50 : 26.4 mg/kg) and diphenylhydantion (ED 50 : ∼ 160 mg/kg). Tolerance to prolongation, i.e., a decrease of the hypnosis time by more than 50% from day 1 to day 5, was most marked with phenobarbital (ED 50 : 12.6 mg/kg) and diphenylhydantion (ED 50 : 113 mg/kg) but was also found with fluconazole (ED 50 : 22.6 mg/kg). Shortened hypnosis times on day 8 occurred with phenobarbital (ED 50 : ∼ 40.0 mg/kg) and diphenylhydantoin (ED 50 : ∼ 160 mg/kg). The antimycotic itraconazole, the antidiarrheal loperamide, the thymosthenic agent ritanserin, and the antiallergics astemizole and levocabastine were devoid of interactions with methohexital. When compared with the basic activity of the tested compounds in rats, interference with methohexital hypnosis was most pronounced with phenobarbital (ratio 3.13) followed by fluconazole (ratio: 3.28) and diphenylhydantoin (ratio: 5.07).