The effect of dihydropyridine calcium channel agents on 5-HT metabolism in the CNS of the rat.
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.
Colado
M I
MI
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Alfaro
M J
MJ
López
F
F
Del Val
V
V
Martín
M I
MI
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester