Interaction of Hallucinogenic Compounds with Cholinergic Receptors

Tetrahydroisoquinoline (TIQ) compounds are plant alkaloids and structurally similar to hallucinogenic agents. We have found that these compounds inhibit cholinergic transmission at the frog neuromuscular junctions. We also observed that they induce contractions and potentiate acetylcholine-induced contractions of the rat ileum. The purpose of this study was to determine the interaction of these compounds with nicotinic and muscarinic acetylcholine receptors. Rat cortical tissues were used for receptor binding assays. In nicotinic receptor binding studies, up to 1 mM, they did not displace α-Bungarotoxin. However, they displaced quinuclidinyl benzilate (QNB) from muscarinic receptor binding sites. The IC₅₀ values of the TIQs varied from 29 to 380 μM. Binding data suggest that they interact with muscarinic but not nicotinic receptors. It is therefore concluded that TIQ compounds inhibit neuromuscular transmission by decreasing acetylcholine release and potentiate smooth muscle contractility by activating muscarinic receptor and possibly other sites. (Supported by NSF R11-8904140)