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Calcium Channel Agonist, (+/-)-Bay K8644, Causes a Transient Increase in Striatal Monoamine Oxidase Activity in Balb/c Mice

Supriti Samantaray, Goutam Chandra, Kochupurackal P Mohanakumar

Neurosci Lett. 2003 May 15;342(1-2):73-6.

PMID: 12727321

Abstract:

We investigated in vivo effects of the L-type calcium channel agonist 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl) phenyl] pyridine-3-carboxylic acid ((+/-)-Bay K8644) on mitochondrial monoamine oxidase (MAO) activity and striatal dopamine (DA) content employing fluorimetric and HPLC-electrochemical procedures, respectively. (+/-)-Bay K8644 administration resulted in visible behavioral dysfunctions in mice. A reversible dose-independent inhibition of striatal DA levels and a significant increase in the brain mitochondrial MAO-A and -B activities were observed in animals treated with the calcium agonist. A positive relationship between the rise in the enzyme activity and decrease in DA content in (+/-)-Bay K8644 treated animals indicates a direct, but transient effect of this channel activator on DA metabolism, which may be related to acute behavioral syndromes exhibited following administration of the drug. Moreover, a direct involvement of L-type dihydropyridine sensitive calcium channels is indicated in this action, since nicardipine could effectively attenuate (+/-)-Bay K8644-induced behavioral aberrations, or block the striatal DA depletion and the increase in MAO activity. The present results have far-reaching implications in neuropharmacological research, where co-treatment of calcium channel drugs and MAO inhibitors are warranted.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP98625264 (S)-(−)-Bay K8644 (S)-(−)-Bay K8644 98625-26-4 Price
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