ABSTRACT
Amantadine, a dopamine agonist is reported to act by releasing dopamine from the dopaminergic nerve terminals as an anti-Parkinsonian drug. In the present behavioural study in the rat, molindone-induced catalepsy and ptosis, which are dopamine dependent-behaviors are reversed by amantadine. Amantadine has also revered molindone-induced inhibition of traction response in mice. Our study indicates that amantadine, like other DA agonists, e.g. amphetamine and apomorphine can antagonize or even reverse the neuroleptic induced dopaminergic behaviors.
Subject(s)
Amantadine/pharmacology , Animals , Behavior, Animal/drug effects , Blepharoptosis/etiology , Catalepsy/chemically induced , Disease Models, Animal , Dopamine/metabolism , Dopamine Agents/pharmacology , Drug Interactions , Male , Mice , Mice, Inbred Strains , Molindone , Probability , Rats , Rats, Inbred Strains , Reference Values , Species SpecificityABSTRACT
Bromocriptine (5-30 mg/kg, ip), 2 hr after administration, induced cage climbing behaviour in mice. Pretreatment with haloperidol, an antagonist of both D-1 and D-2 dopamine receptors, metoclopramide and molindone, the selective D-2 dopamine receptor antagonists, effectively antagonised bromocriptine-induced climbing behaviour. The results indicate that bromocriptine most probably induces climbing behaviour in mice by stimulating the postsynaptic striatal D-2 dopamine receptors.
Subject(s)
Animals , Behavior, Animal/drug effects , Bromocriptine/antagonists & inhibitors , Dose-Response Relationship, Drug , Haloperidol/pharmacology , Male , Metoclopramide/pharmacology , Mice , Molindone/pharmacology , Motor Activity/drug effects , Receptors, Dopamine/drug effects , Receptors, Dopamine D2ABSTRACT
Pretreatment with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, was found to increase the intensity of catalepsy induced by haloperidol, chlorpromazine and molindone. The drug probably decreases the synthesis of dopamine and makes less dopamine available for release and to compete with the neuroleptic for the postsynaptic striatal dopamine receptor sites with resultant potentiation of the neuroleptic-induced catalepsy.
Subject(s)
Animals , Antipsychotic Agents/toxicity , Catalepsy/chemically induced , Chlorpromazine/toxicity , Dopamine/biosynthesis , Drug Synergism , Haloperidol/toxicity , Humans , Male , Methyltyrosines/toxicity , Molindone/toxicity , Rats , alpha-MethyltyrosineABSTRACT
Pretreatment with the neuroleptics, haloperidol and molindone, significantly antagonized the dopamine-induced depressor response in the anaesthetized dogs. The depressor response to dopamine was however, not significantly affected by propranolol, atropine or antazoline pretreatment. The results suggest that molindone like haloperidol, is capable of blocking the vascular dopamine receptors responsible for mediating dopamine-induced vasodilatation in the coeliac, mesenteric and renal vascular bed and fall in blood pressure.