Dm. Wynter-adams et al., Isolation of a muscarinic alkaloid with ocular hypotensive action from Trophis racemosa, PHYTOTHER R, 13(8), 1999, pp. 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 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.