Antidopaminergic action of verapamil and several other drugs: inactivation of vesicular dopamine.
Verapamil was tested for its effect upon dopamine in striatal and olfactory tubercle synaptosomes (P2) in the presence of L-alpha-methyl p-tyrosine, an inhibitor added to block new amine formation. Verapamil significantly potentiated the decline of dopamine in a concentration dependent manner. Several other calcium channel associated drugs such as gallopamil, diltiazem, flunarizin and prenylamine, also enhanced the decline of dopamine. Several agents known for their various dopaminergic actions were tested under the same experimental conditions. Reserpine greatly reduced dopamine levels (greater than 90%) and tetrabenazine was also effective. Amphetamine, nomifensine and apomorphine were without any marked effect. Haloperidol, a potent dopamine (DA-2) antagonist, caused only a weak decrease of dopamine. In contrast, another DA-2 antagonist thioridazine enhanced dopamine loss significantly. These results indicate that verapamil and several other drugs may enhance the inactivation of dopamine present in intraneuronal vesicles.
Bagchi
S P
SP
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962.
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists; D008781:Methyltyrosines / Q000494:pharmacology; D009830:Olfactory Bulb / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology*; D014793:Visual Cortex / Q000378:metabolism*; D019805:alpha-Methyltyrosine
D002120:Calcium Channel Agonists; D018492:Dopamine Antagonists; D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D014700:Verapamil; D014446:Tyrosine 3-Monooxygenase