Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine's positive subjective effects: A preliminary study

Bankole A. Johnson, John D Roache, Patrick S. Bordnick, Nassima Ait-Daoud

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Rationale: 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. Conclusion: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d- methamphetamine dependence.

Original languageEnglish (US)
Pages (from-to)295-300
Number of pages6
JournalPsychopharmacology
Volume144
Issue number3
DOIs
StatePublished - 1999

Fingerprint

Isradipine
Methamphetamine
Calcium Channel Blockers
Placebos
Dopamine
1,4-dihydropyridine
Dextroamphetamine
Therapeutics
Mesencephalon
Reward
Cocaine
Cross-Over Studies
Volunteers

Keywords

  • Calcium channel antagonist
  • Humans
  • Isradipine
  • Methamphetamine
  • Reward
  • Subjective effects

ASJC Scopus subject areas

  • Pharmacology

Cite this

Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine's positive subjective effects : A preliminary study. / Johnson, Bankole A.; Roache, John D; Bordnick, Patrick S.; Ait-Daoud, Nassima.

In: Psychopharmacology, Vol. 144, No. 3, 1999, p. 295-300.

Research output: Contribution to journalArticle

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abstract = "Rationale: 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. Conclusion: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d- methamphetamine dependence.",
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