Effects of isradipine and darodipine on serotonergic system of the rat brain

Pharmacology, Biochemistry, and Behavior
R GaggiA M Gianni

Abstract

Isradipine and darodipine are dihydropyridine calcium antagonists that easily pass into the brain, showing high affinity for cerebral L-type voltage-sensitive calcium channel (VSCC). These drugs were IP administered to rats to study their effects on serotonergic systems of discrete brain areas. Isradipine (0.05-5.0 mg/kg) and darodipine (0.3-20 mg/kg) increased the 5-HIAA/5-HT ratio, mostly enhancing the metabolite (5-HIAA) content in various brain areas, suggesting that serotonin (5-HT) turnover was increased. This increase appeared to depend on facilitation of serotonergic neurotransmission, because low doses of isradipine (< 0.075 mg/kg) or darodipine (< 0.6 mg/kg) enhanced the number of head twitches induced by L-5-hydroxytryptophan (L-5-HTP). However, higher doses of isradipine (1.5 mg/kg) or darodipine (5 mg/kg) also appeared to stimulate a negative feedback mechanism, which predominated over the facilitation when the serotonergic neurotransmission was strongly activated. Thus, higher drug doses decreased both the serotonin turnover and the number of head twitches on rats treated with L-5-HTP. It was speculated that the observed effects were due to brain VSCC blockade, although the studied compounds showed a peculiar prof...Continue Reading

References

Jan 1, 1992·Psychopharmacology·O Pucilowski
Jan 1, 1992·Pharmacology·R GaggiP Roncada
Sep 1, 1991·Trends in Pharmacological Sciences·R W TsienW A Horne
Jun 8, 1990·European Journal of Pharmacology·R Gaggi, A M Gianni
Jan 2, 1987·Science·R J Miller
Jul 1, 1986·British Journal of Pharmacology·F BongianniD E Pellegrini-Giampietro
Apr 28, 1980·Life Sciences·W D Matthews, C D Smith

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Citations

Sep 23, 1997·Pharmacology, Biochemistry, and Behavior·R GaggiP Roncada
Sep 1, 1997·General Pharmacology·R GaggiP Roncada
May 22, 1998·General Pharmacology·S OzyazganA G Akkan
Nov 26, 1999·European Psychiatry : the Journal of the Association of European Psychiatrists·M Hansenne, M Ansseau

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