Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects

• Published in: The international journal of neuropsychopharmacology Vol. 8; no. 2; pp. 203 - 213
• Main Authors: Johnson, Bankole A., Roache, John D., Ait-Daoud, Nassima, Wallace, Christopher, Wells, Lynda, Dawes, Michael, Wang, Yanmei
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.06.2005; Oxford University Press
• Subjects: Adolescent; Adult; Amphetamine-Related Disorders - drug therapy; Amphetamine-Related Disorders - physiopathology; Analysis of Variance; Area Under Curve; Calcium Channel Blockers - therapeutic use; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Routes; Drug Administration Schedule; Female; Humans; Isradipine - therapeutic use; Male; Methamphetamine; Middle Aged; Reinforcement (Psychology); Surveys and Questionnaires; Time Factors; craving; methamphetamine; Calcium-channel antagonist; subjective effects; reinforcement; humans; isradipine
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145704005036

In healthy human volunteers, we have previously shown that isradipine, a dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine-induced positive subjective effects associated with its abuse liability, presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present study, we combined acute immediate-release (IR) isradipine with repeated sustained-release (SR) isradipine pretreatment to determine whether isradipine could antagonize methamphetamine's positive subjective and reinforcing effects in methamphetamine-dependent research subjects. We included 18 non-treatment-seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this double-blind, within-subject, cross-over study, which was done in a human laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on three different days after 5 days of double-blind cross-over treatment with either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self-report questionnaires measured drug liking, euphoria, craving, stimulation, and methamphetamine preference. Methamphetamine reinforcement was measured by a behavioural procedure involving choices between methamphetamine and money. For those who received isradipine second and placebo first as the pretreatment paradigm but not vice versa, methamphetamine-induced drug liking, elation, and preference were reduced significantly by isradipine. Depending upon conditioning status, isradipine can reduce some methamphetamine-induced positive subjective and reinforcing effects associated with its abuse liability in methamphetamine addicts.