ABSTRACT
Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors.
Subject(s)
Chlorpromazine/pharmacology , Dopamine/metabolism , Fluphenazine/pharmacology , Methotrimeprazine/pharmacology , Receptors, Dopamine/drug effects , Animals , Apomorphine/pharmacology , Caudate Nucleus/drug effects , Electric Stimulation , Male , Methotrimeprazine/antagonists & inhibitors , RabbitsABSTRACT
The effectiveness of naloxone hydrochloride in reversing Immobilon anaesthesia was evaluated in 14 dogs. Although a dose rate of 0.02 mg per kg body-weight briefly reversed the respiratory and cardiovascular depression, a dose of at least 0.6 mg per kg body-weight was required before full recovery of consciousness occurred. The action of naloxone was found to be relatively short lived and relapse tended to occur after 10 to 15 minutes. The implications of these findings are discussed in relation to the use of naloxone in the event of accidental self-administration of Immobilon in man.
