Wynter-Adams, D.M.; Simon, Oswald R.; Gossell-Williams, Maxine D.; West, M.E
Author Affiliation, Ana.
Department of Basic Medical Sciences
Isolation of a muscarinic alkaloid with ocular hypotensive action from Trophis racemosa
Date of Publication
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 mL of a 1% solution) and pirenzepine at a non selective antagonist dose (0.1 mL of 0.5% solution) for M1 and M3 receptors blocked the reduction of intra-ocular pressure, but alpha-adrenoceptor blockade with phenoxybenzamine (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 produced contractions which were inhibited by atropine (6 × 10-7M or 0.4 µg/mL) and by pirenzepine at a non-selective antagonist dose (3.1 × 10-6M or 1.3 µg/mL) for M1 and M3 receptors. But neither selective blockade of M2 receptors with gallamine (1.7 × 10-6M or 1.5 µg/mL) nor selective blockade of M1 receptors with pirenzepine (7 × 10-9M or 3 ng/mL) inhibited the alkaloid-induced contractions. There was also no inhibition of the alkaloid-induced contractions in the presence of ganglionic nicotinic receptor blockade with pentolinium (5.6 × 10-7M or 0.3 µg/mL) and hexamethonium (1.7 × 10-6M or 0.6 µg/mL), but nicotine-induced contractions were inhibited by these ganglionic blockers. These results suggest that a muscarinic alkaloid from Trophis racemosa produced ocular hypotension via M3 receptor stimulation in dog....