Effect of M2 muscarinic receptor blockade in rats with haloperidol-produced catatonic syndrome.

We studied the functional role of individual subtypes of muscarinic cholinoceptors in the pathogenesis of neuroleptic parkinsonism in rats. Blockade of M4 receptors prevented the development of extrapyramidal disorders, which was abolished by simultaneous blockade of M2 receptors. The data suggest that various subtypes of muscarinic receptors are involved in the regulation of dopamine concentration.

Qualitative assessment of selective blockade of M(4)-cholinoreceptors in the whole organism.

Quantitative assessment of selective blockade of M4-subtype muscarinic receptors was performed by the number of pilocarpine-induced movements of lower jaw in rats. Three antagonists (atropine, cyclodol, and glipin) were used in the experiments. Glipin produced the most potent blockade of M4 receptors in the whole organism compared to other test antagonist.

[The role of M-cholinoreceptor subtypes in heart rhythm disturbances of various etiology].

The experiments on rats showed different activities of pilocarpine, arecoline, and DDVF in tests for the onset of bradycardia and hypersalivation. A comparative study of the activity of selective M-cholinoblockers in preventing the arrhythmias induced by phosphacol and potassium cyanide showed that the activity of M1-antagonist pirenzepine is higher as compared to that of the M2-antagonist AF-DX-116; at the same time both drugs showed equal activity with respect to arrhythmias induced by aconitine, calcium chloride, and carbachol. It is suggested that the arrhythmias of various etiology involve different subtypes of M-cholinoreceptors.

[Effect of pH on muscarinic antagonist selectivity].

The results of in vitro experiments showed that the receptor selectivity of the M-cholinoblocker tropacin (in contrast to that of amedine) is pH-dependent. A difference observed in the characteristics of tropacin selectivity in vivo and in vitro is probably explained by dissimilar conditions for the ligand interaction with M-cholinoreceptors in the organism and in the in vitro experiments. It is suggested that certain short-time (transient) local pH changes capable of affecting the ligand--receptor interaction parameters may take place in the synaptic cleft in the course of the neurotransmission.

[Effect of biotransformation on the receptor selectivity of muscarinic antagonists in vivo].

In the experiments in vivo it is found that the receptor selectivity of muscarine antagonist glypine is time-dependent unlike atropine, amedine, benzhexol, benactyzine, and thropacin. Using modulation of the metabolic system activity it is shown that upon biotransformation glypine forms active metabolites that differs in receptor selectivity of the action.