Central and peripheral mediation of hypothermia, tremor and salivation induced by muscarinic agonists in mice.

UNLABELLED: Hypothermia, tremor and salivation induced by muscarinic cholinergic agonists were studied in mice. Oxotremorine-M (quarternary agonist) shows high potency after intracerebroventricular administration, but the potency is low after subcutaneous administration. Oxotremorine potency (non-quarternary agonist) is higher after intracerebroventricular administration than after subcutaneous administration. Scopolamine and atropine (non-quarternary antagonists) antagonize oxotremorine-induced effects more potently after intracerebroventricular than subcutaneous administration. The quarternary antagonists N-methylscopolamine (NMS) and N-methylatropine (NMA) potently antagonize oxotremorine-induced salivation after both subcutaneous and intracerebroventricular administration. Hypothermia is antagonized partially (20-40%) over a large dose range after subcutaneous administration. In ex vivo receptor-binding studies of rat brain tissue, oxotremorine, scopolamine and atropine administered subcutaneously dose-dependently displace 3H-oxotremorine-M. Oxotremorine-M and NMS displace 3H-oxotremorine-M by 21% and 35%, respectively; NMA is ineffective. IN
CONCLUSION: Muscarinic cholinergic-mediated tremor is centrally regulated; hypothermia involves both a central and a peripheral component, the peripheral regulation being relatively less important than the central; central and peripheral regulation of salivation are equally important. Penetration of the blood brain barrier by oxotremorine-M and NMS is shown in the ex vivo binding studies.