Isolation of a muscarinic alkaloid with ocular hypotensive action from Trophis racemosa

A muscarinic alkaloid with a quaternary nitrogen was isolated from Trophis racemosa. Aqueous solutions (0.5%-2%) of the chloride salt of the alkaloid produced dose-dependent reductions of intra-ocular pressure ranging from 6. 6 +/- 0.7 mmHg to 15.7 +/- 0.3 mmHg, (p < 0.001, n = 5) in dogs. Atropine ( 0.1 mt of a 1% solution) and pirenzepine at a non selective antagonist dose (0.1 mt of 0.5% solution) for M-1 and M-3 receptors blocked the reduction of intra-ocular pressure, but alpha-adrenoceptor blockade with phenoxybenza mine (0.1 mL of a 1% solution) did not block the reduction of intra-ocular pressure, On the isolated guinea-pig ileum and trachea, the alkaloid produc ed contractions which were inhibited by atropine (6 x 10(-7)M or 0.4 mu g/m L) and by pirenzepine at a non-selective antagonist dose (3.1 x 10(-6),M or 1.3 mu g/mL) for M-1 and M-3 receptors. But neither selective blockade of M-2 receptors with gallamine (1.7 x 10(-6)M or 15 mu g/mL) nor selective bl ockade of M-1 receptors with pirenzepine (7 x 10(-9)M or 3 ng/mL) inhibited the alkaloid-induced contractions, There was also no inhibition of the alk aloid-induced contractions in the presence of ganglionic nicotinic receptor blockade with pentolinium (5.6 x 10(-7)M or 0.3 mu g/mL) and hexamethonium (1.7 x 10(-6)M or 0.6 mu g/mL), but nicotine-induced contractions were inh ibited by these ganglionic blockers, These results suggest that a muscarini c alkaloid from Trophis racemosa produced ocular hypotension via M-3 recept or stimulation in dogs, Copyright (C) 1999 John whey & Sons, Ltd.