The in vitro pharmacology of chloroquine and quinacrine.

The effects of guanethidine, chloroquine and quinacrine on noradrenergic nerves have been compared in vitro using the isolated expansor secundariorum muscle of chicks. The effect of chloroquine on alpha-methyl-noradrenaline uptake by noradrenergic nerve terminals in various tissues were studied. The inhibitory action of guanethidine and quinacrine on noradrenergic nerves appeared to be mediated intraneuronally. The inhibitory action of chloroquine was readily reversible and unaffected by dexamphetamine. Chloroquine caused supersensitivity of the expansor muscle to noradrenaline by blocking its neuronal reuptake since the supersensitivity caused by denervation was not further increased by chloroquine. This was confirmed by the finding that chloroquine inhibited alpha-methylnoradrenaline uptake (Uptake1). Quinacrine did not cause supersensitivity to noradrenaline, possibly due to its direct depressant action on the expansor secundariorum muscle.