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 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 x 10(-7) M or 0.4 microg/mL) and by pirenzepine at a non-selective antagonist dose (3.1 x 10(-6) M or 1.3 microg/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 1.5 microg/mL) nor selective blockade 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 alkaloid-induced contractions in the presence of ganglionic nicotinic receptor blockade with pentolinium (5.6 x 10(-7) M or 0.3 microg/mL) and hexamethonium (1.7 x 10(-6) M or 0.6 microg/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.
Wynter-Adams
D M
DM
Department of Pharmacology, University of the West Indies, Kingston, Jamaica W.I.
Simon
O R
OR
Gossell-Williams
M D
MD
West
M E
ME
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D018727:Muscarinic Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D015814:Ocular Hypotension / Q000139:chemically induced*; D010425:Pentolinium Tartrate / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D014132:Trachea / Q000187:drug effects
D000470:Alkaloids; D000959:Antihypertensive Agents; D018727:Muscarinic Antagonists; D010936:Plant Extracts; D010862:Pilocarpine; D018738:Hexamethonium; D010890:Pirenzepine; D001285:Atropine; D002217:Carbachol; D010425:Pentolinium Tartrate; D000109:Acetylcholine; D005703:Gallamine Triethiodide