Erowid References Database
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Richardson BP, Engel G, Donatsch P.
“In Vitro Pharmacology of Neuronal 5-HT Receptor antagonists”.
Proceedings of the 25th Dutch Federation Meeting. 1984 Apr 17-9.
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Abstract
Gaddum and Picarelli (1957) were thy first to demonstrate 5-HT M-receptors on peripheral neuroses. Since then it has become clear that 5-HT receptors are widely distributed over the peripheral nervous system (see Wallis, 1981). Unfortunately, the pharmacological classification of these receptors has been greatly hindered by the lack of selective agonists or antagonists. In 1979 our group started a project with the aim of developing selective agonists and antagonists for these receptors. The bioassays used were: the rabbit vagus nerve (Neto, 1978), the Langendorff heart and the guinea pig ileum (Fozard et a1 1979). Contractions of the rat uterus and displacement of 3H-5HT and 125-LSD from rat cortex membranes were used to monitor the affinity of compounds for smooth muscle D-receptors and for central 5-HT1 and 5-HT2 binding sites respectively ( et al 1983). Using 5-HT itself as the chemical lead, highly selective agonists for M or D-receptors were obtained by making systemmatic single methyl substitutions in the indole nucleus and ethylamine side chain. By extending the side chain and making semi-rigid analogues where the terminal nitogen was included in a tropine or homotropine ring system, a large series of competitive antagonists of 5-HT M-receptors with amazingly high affinity (PA2 > 15) and selectivity were obtained. Many of these compounds had significantly differing PA2 values for the M-receptors on nerve fibres in the vague, heart and ileum, indicating that the receptors found in these 3 locations are different. None of these antagonists had appreciable affinity for central 5-HT1 or 5-HT2 binding sites or for S-HT autoreceptors found in rat brain cortex slices. Based on these observations, a general classification for 5-HT receptors will be proposed.
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