Behavioral and biochemical effects of a novel calcium antagonist, KB-2796, on the central dopaminergic system.
The effect of a novel calcium antagonist, KB-2796, on the central dopaminergic system was behaviorally and biochemically studied in mice and compared with that of flunarizine, nicardipine and chlorpromazine. Neither KB-2796 nor nicardipine had an inhibitory effect on apomorphine-induced cage climbing and turning behavior in mice with unilateral lesions in the striatum, even at a high dose of 100 mg/kg p.o. Both drugs slightly inhibited methamphetamine-induced increases in locomotor activity and turning behavior but only at a high dose (100 mg/kg p.o.). KB-2796 and nicardipine did not affect the content of dopamine (DA), norepinephrine, and serotonin, or the content of their metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid, or the DA turnover rate in the forebrain of mice. However, flunarizine and chlorpromazine inhibited behavioral changes induced by apomorphine or methamphetamine in a dose-dependent manner, increased the content of DOPAC and HVA and accelerated the DA turnover rate in mouse brain. These results suggest that KB-2796 has a negligible effect on the central dopaminergic system.
Ozaki
A
A
Department of Pharmacology, Kanebo Ltd., Osaka, Japan.
Ikegami
A
A
Yoshidomi
M
M
Yamashita
A
A
Sukamoto
T
T
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D016627:Oxidopamine; D010879:Piperazines / Q000494:pharmacology*
D015306:Biogenic Monoamines; D002121:Calcium Channel Blockers; D010879:Piperazines; D008694:Methamphetamine; D016627:Oxidopamine; C052424:lomerizine; D001058:Apomorphine; D004298:Dopamine