The Involvement of Muscarinic Receptor Subtypes in the Mediation of Hypothermia, Tremor, and Salivation in Male Mice

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Abstract
The potency of centrally administered non‐selective (atropine and N‐methyl scopolamine) and putatively selective muscarinic antagonists (pirenzepine, AF‐DX 116 and 4‐DAMP) in inhibition of oxotremorine‐induced hypothermia, tremor and salivation in male mice has been compared with their potencyin vitroin three functional systems, where muscarinic effects are mediated preferentially by M1(i.e. superior cervical ganglion), M2(i.e. atrium), and M3(i.e. ileum) receptors. Atropine, N‐methyl scopolamine and 4‐DAMP potently abolished the effects of oxotremorine. Pirenzepine abolished tremor and salivation, whereas hypothermia was antagonized partially only. AF‐DX 116 had but weak antagonistic effects. Atropine and N‐methyl scopolamine were potent antagonists in all threein vitrotest systems. High potency was also seen with 4‐DAMP, in particular in the ileum preparation. Pirenzepine showed its highest potency in the ganglion preparation. AF‐DX 116 was a weak and non‐selective antagonist in all threein vitropreparations. Our studies indicate that the muscarinic induction of tremor and salivation may be preferentially mediated by M3receptors whereas both M2and M3receptors may be involved in the mediation of hypothermia. However, the overall conclusion is that compounds with higher receptor subtype selectivity are needed.