alexa Effect of felodipine, a new dihydropyridine vasodilator, on contractile responses to potassium, noradrenaline, and calcium in mesenteric resistance vessels of the rat.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Nyborg NC, Mulvany MJ

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Abstract The effect of felodipine [4-(2,3-dichloro-phenyl)-1,4-dihydro-2,6-dimethyl-3-ethoxycarbonyl-5- methoxycarbonylpyridine on the contractile responses of mesenteric resistance vessels denervated in vitro was investigated. Sustained contractions of this vessel type were totally dependent on extracellular calcium. Felodipine (10-(15)-10-(9)M) had a concentration-dependent inhibitory action on contraction induced by maximal potassium (125 mM) and noradrenaline (10-(5)M) stimulation. Felodipine was more potent and more selective than D600 and nifedipine. Potassium and noradrenaline concentration-response characteristics were insurmountably antagonized by felodipine, the potassium sensitivity of vessels being unaffected while noradrenaline sensitivity was decreased. In calcium-depleted vessels, felodipine in all concentrations tested produced insurmountable antagonism of the potassium-activated calcium concentration-response characteristics, whereas the antagonism in low concentrations (10-(15)-10-(11)M) was surmountable in noradrenaline-activated vessels. Felodipine 10-(9) M blocked the response of potassium-activated vessels almost completely, whereas approximately 50\% of the response of noradrenaline-activated vessels persisted. The results of this investigation indicate that the effect of felodipine may be caused primarily by selective inhibiton of responses evoked by membrane depolarization.
This article was published in J Cardiovasc Pharmacol and referenced in Journal of Bioequivalence & Bioavailability

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