Transdermal selegiline and intravenous cocaine: safety and interactions.
BACKGROUND
Because the dopamine system appears to be involved in both acute and chronic effects of cocaine, medication development efforts for cocaine addiction have focused largely on agents that interact with the dopamine system. Selegiline, a selective monoamine oxidase B inhibitor, indirectly modulates dopamine levels, and research suggests selegiline may modify subjective effects of cocaine.


OBJECTIVE
To evaluate further the safety and potential of transdermal selegiline as a treatment for cocaine dependence, interactions between transdermal selegiline and intravenous cocaine were studied in cocaine-dependent volunteers.


METHODS
Pharmacokinetics and subjective, physiological, and endocrinological effects of intravenous cocaine (0,20 and 40 mg) were evaluated both before and during transdermal selegiline treatment (20 mg/day, 10 days) in 12 cocaine-dependent subjects. A transdermal selegiline formulation was used to avoid the risks associated with oral administration of MAO inhibitors.


RESULTS
Selegiline attenuated some physiological (systolic blood pressure and heart rate) and subjective (good effects, liking, stimulated, high, desire for cocaine) effects of cocaine. Selegiline did not affect cocaine's pharmacokinetics or cocaine-induced prolactin decrease and growth hormone increase.


CONCLUSIONS
The combined administration of the transdermal selegiline patch and up to 40 mg cocaine was well tolerated. Selegiline may reduce physiological and subjective effects of cocaine. A randomized trial is needed to evaluate the efficacy of selegiline for cocaine abuse.
Houtsmuller
Elisabeth J
EJ
Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Bayview Medical Center, 5510 Nathan Shock Drive, Baltimore, MD 21224-6823, USA. ehoutsm@jhmi.edu
Notes
Lisa D
LD
Newton
Thomas
T
van Sluis
Nicolette
N
Chiang
Nora
N
Elkashef
Ahmed
A
Bigelow
George E
GE
D000279:Administration, Cutaneous; D000328:Adult; D003042:Cocaine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011388:Prolactin / Q000097:blood; D012642:Selegiline / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D011388:Prolactin; D013006:Growth Hormone; D008995:Monoamine Oxidase; D003042:Cocaine