Research article

A Phase 1 Trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion

Debra S Harris^1,2 , Thomas Everhart³ , Peyton Jacob III³ , Emil Lin⁴ , John E Mendelson⁵ and Reese T Jones³

¹Department of Psychiatry, University of Cincinnati, OH, USA

²Cincinnati VA Medical Center, OH 45220, USA

³Drug Dependence Research Center, University of California, San Francisco, USA

⁴Drug Studies Unit, University of California, San Francisco, USA

⁵Addiction Pharmacology Research Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA, USA

author email corresponding author email

BMC Clinical Pharmacology 2009, 9:13doi:10.1186/1472-6904-9-13

Published:	1 August 2009

Abstract

Background

The selective MAO-B inhibitor selegiline has been evaluated in clinical trials as a potential medication for the treatment of cocaine dependence. This study evaluated the safety of and pharmacologic interactions between 7 days of transdermal selegiline dosed with patches (Selegiline Transdermal System, STS) that deliver 6 mg/24 hours and 2.5 mg/kg of cocaine administered over 4 hours.

Methods

Twelve nondependent cocaine-experienced subjects received deuterium-labeled cocaine-d5 intravenously (IV) 0.5 mg/kg over 10 minutes followed by 2 mg/kg over 4 hours before and after one week of transdermal selegiline 6 mg/24 hours. Plasma and urine were collected for analysis of selegiline, cocaine, catecholamine and metabolite concentrations. Pharmacodynamic measures were obtained.

Results

Selegiline did not change cocaine pharmacokinetic parameters. Selegiline administration increased phenylethylamine (PEA) urinary excretion and decreased urinary MHPG-sulfate concentration after cocaine when compared to cocaine alone. No serious adverse effects occurred with the combination of selegiline and cocaine, and cocaine-induced physiological effects were unchanged after selegiline. Only 1 peak subjective cocaine effects rating changed, and only a few subjective ratings decreased across time after selegiline.

Conclusion

No pharmacological interaction occurred between selegiline and a substantial dose of intravenous cocaine, suggesting the combination will be safe in pharmacotherapy trials. Selegiline produced few changes in subjective response to the cocaine challenge perhaps because of some psychoactive neurotransmitters changing in opposite directions.