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Appetite‐modulating drugs in dwarf goats, with special emphasis on benzodiazepine‐induced hyperphagia and its antagonism by flumazenil and R° 15–3505
Author(s) -
MIERT A.S.J.P.A.M. VAN,
KOOT M.,
DUIN C. T. M. VAN
Publication year - 1989
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1989.tb00656.x
Subject(s) - flumazenil , diazepam , benzodiazepine , (+) naloxone , antagonism , antagonist , medicine , endocrinology , pharmacology , chemistry , receptor
In dwarf goats fasted for 2 h, i.v. administration of the benzodiazepine (BZ) agonists diazepam (60 μg/kg), brotizolam (2 and 4 μg/kg) and climazolam (100 μg/kg) induced hyperphagic effects, whereas i.v. injections of the BZ‐antagonist flumazenil (R°15–1788; 0.5 mg/kg), the anthelmintic ivermectin (0.1 mg/kg), the 5‐HT2 antagonist ritanserine (0.1 mg/kg), ACTH (10 μg/kg) and prednisolone (1 mg/kg) were inactive in a 30‐min feeding test. Both the BZ‐antagonist R°15–3505 (≤ 0.1 mg/kg) and the opiate receptor antagonist naloxone (0.1 mg/kg) had anorectic effects in dwarf goats given 30 min access to a palatable pelleted concentrate. The hyperphagic effects of climazolam and brotizolam were not antagonized by flumazenil, whereas similar doses of this drug completely reversed muscle incoordination and ataxia induced by much higher doses of these BZ‐agonists. In the combination experiments with naloxone and BZ‐agonists, naloxone antagonized the hyperphagic effects of both diazepam and brotizolam. Similarly, in the diazepam–R°15–3505 study, there was a significant effect of diazepam and a significant inhibition of this effect by R° 15–3505 (50 μg/kg). In the diazepam–ivermectin combination experiment no evidence for drug potentiation was found. These results and the mode of action of the above mentioned drugs are discussed in relation to feeding behaviour.