Pharmacological evaluation of N-methyl-actinodaphnine, a new vascular α-adrenoceptor antagonist, isolated from Illigera luzonensis

The pharmacological activity of N-methyl-actinodaphnine, isolated from Illigera luzonensis, was determined by functional and binding experiments with peripheral tissues. In a functional study, N-methyl-actinodaphnine was a simple competitive antagonist of contractions elicited by phenylephrine (pA 2...

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Bibliographic Details
Published in:European journal of pharmacology 1995-06, Vol.279 (1), p.33-41
Main Authors: Guh, Jih-Hwa, Ko, Feng-Nien, Yu, Sheu-Meei, Wu, Yang-Chang, Teng, Che-Ming
Format: Article
Language:English
Subjects:
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists - isolation & purification
Adrenergic alpha-Antagonists - pharmacology
Animals
Aorta - drug effects
Biological and medical sciences
Cells, Cultured
Dioxolanes - isolation & purification
Dioxolanes - pharmacology
Drugs, Chinese Herbal - isolation & purification
Drugs, Chinese Herbal - pharmacology
Female
General pharmacology
Guinea Pigs
Illigera luzonensis
Inositol Phosphates - analysis
Male
Medical sciences
Muscle Contraction - drug effects
Muscle, Smooth, Vascular - drug effects
N-Methyl-actinodaphnine
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Piperazines - pharmacology
Prazosin - pharmacology
Rats
Rats, Wistar
Spleen - drug effects
Trachea - drug effects
Vas Deferens - drug effects
α-Adrenoceptor antagonist
α1-Adrenoceptor subtype
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Summary:The pharmacological activity of N-methyl-actinodaphnine, isolated from Illigera luzonensis, was determined by functional and binding experiments with peripheral tissues. In a functional study, N-methyl-actinodaphnine was a simple competitive antagonist of contractions elicited by phenylephrine (pA 2 = 7.11) in rat thoracic aorta; it also competitively antagonised the clonidine-induced inhibition of the twitch response of rat vas deferens (pA 2 = 5.01). In addition, [ 3H]inositol monophosphate formation caused by noradrenaline (3 μM) in rat isolated thoracic aorta was concentration dependently inhibited by N-methyl-actinodaphnine (1 and 10 μM); however, it had no effect on cyclic AMP and cyclic GMP contents. Additionally, N-methyl-actinodaphnine had extremely low affinity for thromboxane receptors, prostaglandin receptors, Ca 2+ channels, muscarinic receptors, histamine receptors, β-adrenoceptors, neurokinin and leukotriene receptors in vitro. However, N-methyl-actinodaphnine also possessed 5-hydroxytryptamine (5-HT) receptor blocking activity. Its potency for blocking 5-HT receptors was about 14 times less than that for blocking α 1-adrenoceptors. In binding experiments, N-methyl-actinodaphnine displaced biphasically the binding of 0.2 nM [ 3H]prazosin to cultured A10 cells. The selectivity for α 1-adrenoceptor subtypes was also investigated in rat vas deferens and spleens. The contractile response in rat vas deferens to noradrenaline was competitively inhibited by N-methyl-actinodaphnine with a pA 2 value of 6.58; N-methyl-actinodaphnine also competitively antagonized the phenylephrine-induced contraction in rat spleen with a pA 2 value of 7.38. These results indicate that N-methyl-actinodaphnine is a selective α 1-adrenoceptor antagonist. Furthermore, it is more selective for the α 1B- than for the α 1A-adrenoceptor subtype.
ISSN:0014-2999
1879-0712
DOI:10.1016/0014-2999(95)00135-8