In vitro effects of gallamine on dissociation kinetics of (3H)N-methylscopolamine and (3H)pirenzepine from rat brain muscarinic receptors.
Gallamine inhibited the binding of both (3H)N-Methylscopolamine ((3H)NMS) and (3H)Pirenzepine ((3H)PZ) in the hippocampus, striatum and cortex of rat brain. Competition curves between gallamine and (3H)PZ suggested that gallamine recognized an homogeneous class of receptors (Hill coefficient close to 1) whereas competition curves, using (3H)NMS as tracer, were compatible with two classes of gallamine receptors (Hill coefficient below 0.7). The latter phenomenon could be explained, at least partially, by the inhibitory effect exerted by gallamine on the k off of (3H)NMS. This effect was already observed at a 10 microM gallamine concentration and reached 100% at 1 mM (a gallamine concentration reducing the k off of (3H)PZ by 30% only). The nature of the radioligand rather than the relative abundance of M1 - M2 receptors was probably responsible for this discrepancy. Gallamine inhibited the (3H)NMS dissociation rate from brain M1 and M2 receptors (i.e. receptors with high and intermediate affinity for pirenzepine) with a lower potency than from cardiac M2 receptors (i.e. receptors with low affinity for pirenzepine).
D000818:Animals; D001285:Atropine / Q000378:metabolism; D001570:Benzodiazepinones / Q000378:metabolism*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019832:N-Methylscopolamine; D010890:Pirenzepine; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism*; D013379:Substrate Specificity
D001570:Benzodiazepinones; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010890:Pirenzepine; D001285:Atropine; D005703:Gallamine Triethiodide; D019832:N-Methylscopolamine