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Pharmacological activity of (−)‐discretamine, a novel vascular α‐adrenoceptor and 5‐hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens
Author(s) -
Ko FengNien,
Yu SheuMeei,
Su MingJai,
Wu YangChang,
Teng CheMing
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13895.x
Subject(s) - medicine , endocrinology , phentolamine , vasoconstriction , prazosin , phenylephrine , yohimbine , phenoxybenzamine , carbachol , angiotensin ii , chemistry , biology , antagonist , receptor , blood pressure
1 The pharmacological activity of (−)‐discretamine, isolated from Fissistigma glaucescens , was determined in rat isolated thoracic aorta, cardiac tissues and ventricular myocytes and guinea‐pig isolated trachea. 2 (−)‐Discretamine was found to be an α 1 ‐adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline (pA 2 = 7.20 ± 0.10)‐ or phenylephrine (pA 2 = 7.60 ± 0.09)‐induced vasoconstriction. It was as potent as phentolamine (pA 2 = 7.51 ± 0.10), but was more potent than yohimbine (pA 2 = 6.18 ± 0.06). Removal of endothelium significantly increased the antagonistic potency of (−)‐discretamine on noradrenaline (pA 2 = 7.52 ± 0.09)‐ or phenylephrine (pA 2 = 7.90 ± 0.09)‐induced vasoconstriction. 3 (−)‐Discretamine was also an α 2 ‐adrenoceptor blocking agent (pA 2 = 6.30 ± 0.15) and a 5‐hydroxytryptamine antagonist (pA 2 = 6.87 ± 0.06), both in rat aorta denuded of endothelium. 4 (−)‐Discretamine protected α‐adrenoceptors from alkylation by the irreversible blocking agent, phenoxybenzamine. 5 [ 3 H]‐inositol monophosphate formation caused by noradrenaline (3 μ m ) in rat thoracic aorta was suppressed by (−)‐discretamine (10 and 30 μ m ) and prazosin (3 μ m ). 6 A high concentration of (−)‐discretamine (30 μ m ) did not affect the contraction induced by the thromboxane receptor agonist U‐46619, prostaglandin F 2α (PGF 2α ), angiotensin II, high K + or endothelin in rat aorta denuded of endothelium. Neither cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by (−)‐discretamine. 7 Contraction of guinea‐pig trachea caused by histamine, leukotriene C 4 or carbachol was not affected by (−)‐discretamine (30 μ m ). (−)‐Discretamine also did not block β 1 or β 2 ‐adrenoceptor‐mediated responses induced by isoprenaline in rat right atria and guinea‐pig trachea. 8 A voltage clamp study in rat ventricular single myocytes revealed that sodium inward current, slow inward Ca 2+ current or transient ( I to ) and steady state ( I 800 ) outward current was not affected by (−)‐discretamine (30 μ m ). 9 It is concluded that (−)‐discretamine is a selective α‐adrenoceptor and 5‐HT receptor antagonist in vascular smooth muscle.