Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine's positive subjective effects: a preliminary study.
BACKGROUND
Dopamine (DA) pathways in the midbrain mediate d-methamphetamine's rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by isradipine.


OBJECTIVE
We studied the effects of high dose isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively).


METHODS
Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers received each of the following six treatments separated by a rest period of 2-7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose isradipine+placebo); e) low-dose d-methamphetamine+high dose isradipine, and f) high-dose d-methamphetamine+high dose isradipine.


RESULTS
d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine.


CONCLUSIONS
Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.
Johnson
B A
BA
University of Texas, Health Science Center at San Antonio, 78284-7792, USA. bjohnson@uthscsa.edu
Roache
J D
JD
Bordnick
P S
PS
Ait-Daoud
N
N
D018663:Adrenergic Agents / Q000494:pharmacology*; D000328:Adult; D000339:Affect / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D004336:Drug Antagonism; D005260:Female; D006801:Humans; D017275:Isradipine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008875:Middle Aged; D012054:Reinforcement, Psychology; D012201:Reward; D019966:Substance-Related Disorders / Q000188:drug therapy
D018663:Adrenergic Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008694:Methamphetamine; C038806:1,4-dihydropyridine; D017275:Isradipine