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Abstract #5819 Published in IGR 2-1
Isolation of a muscarinic alkaloid with ocular hypotensive action from Trophis racemosa
Wynter-Adams DM; Simon OR; Gossell-Williams MD; West MEPhytotherapy Research 1999; 13:670-674
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 intraocular 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 M(1) and M(3) receptors blocked the reduction of intraocular pressure, but α-adrenoceptor blockade with phenoxybenzamine (0.1 ml of a 1% solution) did not block the reduction of intraocular pressure. On the isolated guinea-pig ileum and trachea, the alkaloid produced contractions which were inhibited by atropine (6x10-7 M or 0.4 μg/ml) and by pirenzepine at a non-selective antagonist dose (3.1x10-6 M or 1.3 μg/ml) for M(1) and M(3) receptors. But neither selective blockade of M(2) receptors with gallamine (1.7x10-6 M or 1.5 μg/ml) nor selective blockade of M(1) receptors with pirenzepine (7x10-9 M 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 (5.6x10-7 M or 0.3 μg/ml) and hexamethonium (1.7x10-6 M 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 M(3) receptor stimulation in dogs.
Dr. D.M. Wynter-Adams, Department of Pharmacology, University of the West Indies, Kingston, Jamaica, W.I.
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
