Effects of Ca2+ channel blockers on physical dependence on diazepam in mice.
The effects of Ca2+ channel blockers on the development of physical dependence on diazepam were examined in mice. Co-administration of flunarizine (T-type Ca2+ channel sensitive blocker), but not of either nifedipine or diltiazem (L-type Ca2+ channel sensitive blockers), with diazepam significantly suppressed the hypersensitivity to FG 7142 following chronic treatment with diazepam. The hypersensitivity to FG 7142 may reflect benzodiazepine withdrawal convulsions. These results suggest that flunarizine, but not nifedipine or diltiazem, may suppress the development of physical dependence on diazepam, and that T-type Ca2+ channels in the brain, rather than L-type Ca2+ channels, may be involved in the development of physical dependence on diazepam.
Mizoguchi
H
H
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Yoshiike
M
M
Suzuki
T
T
Misawa
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam; D004110:Diltiazem / Q000493:pharmacokinetics / Q000494:pharmacology; D004347:Drug Interactions; D005444:Flunarizine / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009543:Nifedipine / Q000493:pharmacokinetics / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D019966:Substance-Related Disorders / Q000188:drug therapy*
D002121:Calcium Channel Blockers; D002243:Carbolines; D011963:Receptors, GABA-A; C035874:FG 7142; D004110:Diltiazem; D009543:Nifedipine; D003975:Diazepam; D005444:Flunarizine