Blockade by pimozide of a noradrenaline sensitive adenylate cyclase in the limbic forebrain: possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics
Blumberg, J.B.; Taylor, R.E.; Sulser, F.
Journal of Pharmacy and Pharmacology 27(2): 125-128
1975
ISSN/ISBN: 0022-3573 PMID: 237072 Document Number: 90696
Noradrenaline AMP in rats. Dopamine and 5-HT (5-hydroxytryptamine) were without effect at all concentrations tested. The presumptive selective dopamine blocker pimozide, when added to the incubation medium for 14 min before the addition of NA, caused a dose-dependent inhibition of this specific noradrenergic cAMP response while not changing the basal level of the cyclic nucleotide. The increase in the cAMP caused by 5 .times. 10-6 M NA was reduced by 50% in the presence of 7.5 .times. 10-8 M pimozide. Pimozide (10-3 to 10-6 M) did not significantly change the activity of cAMP phosphodiesterase in vitro preparations from the limbic forebrain. The drug's effect on the NA-induced accumulation of cAMP is the consequence of an inhibition of the NA specific adenylate cyclase.