Isolation of a muscarinic alkaloid with ocular hypotensive action from Trophis racemosa
✍ Scribed by D.-M. Wynter-Adams; O. R. Simon; M. D. Gossell-Williams; M. E. West
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 92 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0951-418X
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✦ Synopsis
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 AE 0.7 mmHg to 15.7 AE 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 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 Â 10 À7 M or 0.4 mg/mL) and by pirenzepine at a non-selective antagonist dose (3.1 Â 10 À6 M or 1.3 mg/ mL) for M 1 and M 3 receptors. But neither selective blockade of M 2 receptors with gallamine (1.7 Â 10 À6 M or 1.5 mg/mL) nor selective blockade of M 1 receptors with pirenzepine (7 Â 10 À9 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 (5.6 Â 10 À7 M or 0.3 mg/mL) and hexamethonium (1.7 Â 10 À6 M or 0.6 mg/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.