Effects of T-type calcium channel blockers on a parkinsonian tremor model in rats.
T-type calcium channels are strongly associated with the generation of rhythmic firing patterns in the CNS. Blockers of these channels may have therapeutic potential for treating various types of tremor. The present study aimed to study the effects of a range of T-type calcium channel blockers in a parkinsonian tremor model in rats. We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor. Among the tested drugs, only ZNS and NCC 55-0396 significantly suppressed TJMs when given at a non-sedating dose. The transitivity of drugs to the central nervous system (CNS) may at least partially explain their differential anti-TJM effects. However, further studies are necessary to reveal other factors, since ethosuximide failed to show anti-TJM effects despite being known to cross the blood brain barrier. The present results suggest that T-type calcium channels in the CNS may be a suitable target for developing new therapeutic strategies for treating parkinsonian tremor.
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan. h-miwa@wakayama-med.ac.jp
Hideto
H
Miwa
Jinsoo
J
Koh
Yoshinori
Y
Kajimoto
Tomoyoshi
T
Kondo
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014202:Tremor / Q000188:drug therapy*
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type