Effects of repeated-dose isradipine on the abuse liability of cocaine.
Despite preclinical studies suggesting that isradipine may antagonize the abuse liability of cocaine, pretreatment with sustained-release isradipine did not reduce euphoric mood in cocaine-using volunteers. This double-blind, within-subject, crossover laboratory study determined whether maximal dose-loading with isradipine could antagonize effects of cocaine in 12 cocaine-dependent research volunteers administered intravenous cocaine doses (0, 0.325, and 0.65 mg/kg) on different days after 5 days of treatment with isradipine or placebo. Isradipine dose was 30 mg sustained release nightly plus 15 mg immediate release 2 hr before cocaine infusion. Cocaine produced dose-related increases in cocaine's subjective effects and a behavioral measure of reinforcement. Isradipine enhanced, rather than antagonized, subjective effects, indicating that isradipine does not antagonize cocaine's abuse liability in dependent research volunteers.
Roache
John D
JD
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, 78229, USA. roache@uthscsa.edu
Johnson
Bankole A
BA
Ait-Daoud
Nassima
N
Mauldin
James B
JB
Thornton
Joe E
JE
Wells
Lynda T
LT
Murff
William L
WL
D000082:Acetaminophen / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000517:prevention & control / Q000523:psychology; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D005059:Euphoria / Q000187:drug effects; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D017275:Isradipine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D013607:Tablets; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D013607:Tablets; D000082:Acetaminophen; D003042:Cocaine; D017275:Isradipine