Comparison of the effects of chloroquine quinacrine and quinidine on autonomic neuroeffector mechanisms.
The in vitro effects of 3 antimalarial compounds (chloroquine, quinacrine and quinidine) on 3 components of the autonomic nervous system have been investigated. The expansor secundariorum muscle was used for studying noradrenergic mechanisms, the chick oesophagus for cholinergic mechanisms, the rat bladder for "purinergic" mechanisms, and the mouse ileum for prostaglandin-mediated responses. Chloroquine reduced responses to noradrenergic and "purinergic" nerve stimulation to similar extents, possibly due to a non-specific effect; it induced supersensitivity to exogenous noradrenaline. Both chloroquine and quinacrine had atropine-like actions in concentrations up to 1 X 10(-4)M; larger concentrations had a direct depressant action on smooth muscle. Quinacrine blocked noradrenergic nerves in a similar fashion to guanethidine but failed to induce supersensitivity to exogenous noradrenaline; it was a potent antagonist of the responses to "purinergic" nerve stimulation. Quinidine blocked responses to "purinergic" nerve stimulation, caused moderate antagonism of alpha-adrenoceptor-mediated effects, but was a weak muscarinic receptor antagonist. The antimalarial compounds were more potent antagonists of prostaglandin-mediated responses than of "purinergic" responses. However, not all their actions could be attributed to prostaglandin antagonism.
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D002645:Chickens; D002738:Chloroquine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D011950:Receptors, Cholinergic; D013779:Tetrodotoxin; D002738:Chloroquine; D011796:Quinacrine; D011802:Quinidine; D009638:Norepinephrine; D007213:Indomethacin