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Eur J Pharmacol. 1989 Feb 7;160(3):339-47.

Central and peripheral effects of the dihydropyridine calcium channel activator BAY K 8644 in the rat.

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1
Merrell Dow Research Institute, Strasbourg, France.

Abstract

Following intraperitoneal (i.p.) administration BAY K 8644 (0.5-4 mg/kg) induced an increase in blood pressure associated with bradycardia, increased tail-flick latency in response to radiant heat, decreased locomotion, induced muscle contraction, postural changes and also reduced reflex activity. Only the postural changes and reduced locomotion were seen after intracerebroventricular administration (5-20 micrograms/kg), suggesting that the other effects are mediated peripherally. All the above effects were antagonised by the calcium channel blocker nifedipine. BAY K 8644 (4 mg/kg i.p.) also significantly increased homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations in the cortex and striatum, an effect which could also be reversed by nifedipine. Apart from inducing hypotension and tachycardia, nifedipine alone had no effect on any of the above parameters. The analgesic-like activity of BAY K 8644 observed in the tail-flick test appears to be related to its vasoconstrictor effects as the peripherally acting vasodilator phenylephrine had similar analgesic activity. These results show that both central and peripheral dihydropyridine-sensitive calcium channels mediate the effects of BAY K 8644. Although a physiological role for the dihydropyridine-sensitive voltage-operated calcium channel in the CNS remains to be demonstrated, activation of these channels can clearly have functional effects.

PMID:
2469593
DOI:
10.1016/0014-2999(89)90089-7
[Indexed for MEDLINE]

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