The effects of arvanil (N-arachidonoyl-vanillyl-amine), a structural hybrid between capsaicin and anandamide, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. Arvanil (0.2-50 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Arvanil produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of arvanil-induced inhibition of I(Ca,L) was 2 microM. Arvanil (5 microM) could shift the steady-state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. No effect of arvanil (20 microM) on delayed rectifier K(+) current (I(K(DR))) was observed; however, capsaicin (20 microM), glyceryl nonivamide (20 microM) and capsinolol (20 microM) suppressed it significantly. Arvanil (20 microM) caused a slight reduction in the amplitude of erg (ether-à-go-go-related)-mediated K(+) current (I(K(erg))) without modifying the activation curve of this current, while capsaicin and glyceryl nonivamide were more effective in suppressing I(K(erg)). Under current-clamp configuration, arvanil decreased the firing frequency of action potentials. Arvanil-mediated inhibition of I(Ca,L) appeared to be independent of its binding to either vanilloid or cannabinoid receptors. The channel-blocking properties of arvanil may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

2002-06-01·Journal of Cardiovascular Pharmacology4区 · 医学

Vanillylamide-Based Propanolamine Derivative Displays α/β-Adrenoceptor Blocking and Vasodilating Properties

4区 · 医学

Article

作者: Yeh, Jwu-Lai ; Lin, Young-Tso ; Wu, Jiunn-Ren ; Lo, Yi-Ching ; Chen, Yea-Wen ; Chiu, Chaw-Chi ; Cheng, Chang-Jenq ; Chen, Ing-Jun

A propanolamine derivative with vanillylamide base, KMUP 880602, was first investigated under in vivo and in vitro conditions. IV KMUP 880602 (0.1, 0.5, 1.0, and 2.0 mg/kg) produced dose-dependent hypotensive and bradycardia responses in pentobarbital-anesthetized Wistar rats. KMUP 880602 also markedly inhibited both the tachycardia effects induced by (-)isoproterenol and arterial pressor responses induced by phenylephrine. In isolated guinea pig tissues, KMUP 880602 competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses. The apparent pA2 values KMUP 880602 were 7.24 +/- 0.08 (right atria), 7.42 +/- 0.07 (left atria), and 6.24 +/- 0.06 (trachea). KMUP 880602 also produced a competitive antagonism of norepinephrine-induced contraction in the isolated rat aorta with pA2 values of 7.64 +/- 0.18. In the radioligand-binding assay, [3H]CGP-12177 binding to rat ventricle and lung tissues and [3H]prazosin binding to brain membranes were inhibited by KMUP 880602 with pKi values of 7.27, 6.08, and 8.25, respectively. In isolated rat thoracic aorta, the vasorelaxant effects of KMUP 880602 on phenylephrine-induced contractions were attenuated by pretreatment with tetraethylammonium (10-3 M) and charybdotoxin (10-7 M) but not by glibenclamide, 4-aminopyridine, and apamin. In conclusion, KMUP 880602 is an alpha/beta-adrenoceptor blocker, with selective beta1-adrenoceptor blocking and vascular smooth muscle relaxation activities. Particularly, the vasorelaxant effect of KMUP 880602 is partially mediated by the opening of charybdotoxin-sensitive K+ channel.

1998-08-01·General Pharmacology: The Vascular System

Ionic Effects of Capsinolol, a Calcitonin Gene-Related Peptide Releasing β-Adrenoceptor Blocker, on Isolated Cardiac Muscles

Article

作者: Lin ; Jwu-Lai Yeh ; Jiunn-Ren Wu ; Ing-Jun Chen

1. Capsinolol (1.0-30.0 microM) in a cumulating manner decreased the maximum upstroke velocity (Vmax), the action potential amplitude and twitch tension in isolated guinea-pig atria and papillary muscle, rabbit papillary muscle, dog Purkinje fibers and human ventricle tissues. 2. In the isolated guinea-pig atrium, perfusing with capsinolol at 3 microM for 3 min temporarily increased the twitch force and decreased spontaneous cycle length; however, the results were reversed after longer exposure of the tissue. 3. Capsinolol prolonged the duration of action potential in the guinea-pig atrium and rabbit papillary muscles. The maximum diastolic potential was shifted to a less-negative level in dog Purkinje fibers and human ventricular muscles.

100 项与 Capsinolol 相关的药物交易

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