Muscarinic receptors pharmacological identification

The debut of the selective AChR agonist (+)-anatoxin-a has provided a new tool for AChR physiology and pharmacology. (+)-Anatoxin not only has high affinity for the nicotinic AChR but it also has high selectivity for nicotinic over muscarinic receptors in the mammalian CNS. Recently, the use of (+)-anatoxin-a was essential to the identification of nicotinic receptors on cultured neurons (4), We are studying the features which allow it to bind with high affinity to the peripheral and central nicotinic receptors and the kinetic effects on receptor conformational... 

The identification of multiple muscarinic receptor subtypes has stimulated the search for ligands with selectivity for a given receptor subtype [34-36]. Five different subt rpes (mi-ms) have been identified so far by molecular cloning. Muscarinic receptors that have been characterized pharmacologically and classified as M1-M4, appear to correspond to cloned m]-m4 receptors. At present, little information is available about the nature and the cellular location of the m5 subtype. 

M1/M4, 41. Thus, spirotramine appears to be superior to pirenzepine in discriminating Mi and M4, and Mi and M3 muscarinic receptor subtypes. The fact that the antagonists currently used to classify muscarinic receptors lack a clear subtype selectivity may explain the difficulties to characterize with classic pharmacological studies the five cloned muscarinic receptors. The results presented in this paper clearly show that the use of tripitramine combined with that of spirotramine, which is able to discriminate between Mi and M4, might eventually allow the pharmacological identification of muscarinic receptor subtypes. 

Gilbert, R., Rattan, S., Goyal, R.K., 1984. Pharmacologic identification, activation and antagonism of two muscarinic sensitive receptor sub-types in the lower oesophageal sphincter. J. Pharmacol. Exp. Ther. 230, 284-291. 

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