The effect of dihydropyridine calcium channel agents on 5-HT metabolism in the CNS of the rat

Abstract

The effects of dihydropyridines on the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxy-3-indole acetic acid (5-HIAA) in the spinal cord and various brain regions of the rat have been studied. Nimodipine, nitrendipine and nifedipine (10 mg kg-1), nisoldipine (5 mg kg-1), and BAY K8644 (0.2 and 2 mg kg-1) were administered i.p. 1 h before killing. The administration of nifedipine and nitrendipine increased 5-HT turnover in all of the areas studied except for the spinal cord. Nisoldipine increased 5-HT turnover in midbrain, hippocampus and cortex, while the effect of nimodipine was restricted to midbrain. BAY K8644 at 2 mg kg-1 produced the same effects as nifedipine and nitrendipine; however, at low doses (0.2 mg kg-1), this compound increased 5-HT turnover only in midbrain and medulla oblongata. These results indicate that both dihydropyridine calcium channel agonist and antagonists are able to activate the 5-HT-ergic system in the central nervous system of the rat in-vivo. Therefore, it seems likely that such effects could be due to indirect actions or to interactions of the compounds with receptors other than the voltage-sensitive calcium channels.

Nifedipine-morphine interaction: a further investigation on nociception and locomotor activity in mice

“…In the locomotor activity test, nifedipine decreased activity in both strains, reduced the hypermotility induced by morphine in the C57 strain and enhanced the locomotor depression produced by the opiate in DBA mice. Failure of nifedipine to affect mouse responses in the radial heat tail-flick test is in agreement with previous findings indicating that calcium-channel blockers produce antinociception in the acetic acid-induced abdominal constriction test (Del Pozo et al 1987;Ohnishi et al 1988), but not in the hot-plate test, another test based on thermal stimulation (Benedek & Szikszay 1984;Hoffmeister & Tettenborn 1986;Contreras et a1 1988 (Swanson & Green 1986;Colado et al 1991). The present findings suggest that haemodynamic factors may be involved in the nifedipine-morphine interaction, since nifedipine and hydralazine exerted similar effects, when combined with the opiate, in the tail-flick test.…”

Modulation of the Antipsychotic Effect of Ziprasidone with Nimodipine

“…It has also been suggested that these substances are closely associated with emotional processes. It has been shown that dihydropyridine calcium channel inhibitors play a role in release of neurotransmitters like acetylcholine, serotonin, dopamine and noradrenaline in the brain and that they activate serotonergic systems in rat brain (23,24). It has been reported that nimodipine activates serotonergic transmission via 5-HT1A receptor blockade and also that activation of 5-HT1A receptors inhibits the calcium current through calcium channels (23,25).…”