%0 Journal Article
%T A Phase 1 Trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion
%A Debra S Harris
%A Thomas Everhart
%A Peyton Jacob
%A Emil Lin
%A John E Mendelson
%A Reese T Jones
%J BMC Pharmacology and Toxicology
%D 2009
%I BioMed Central
%R 10.1186/1472-6904-9-13
%X 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.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.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.The acute administration of cocaine produces euphoria and chronic administration produces hedonic dysregulation, which are both believed to be mediated by dopaminergic systems [1]. Chronic cocaine use-induced dysregulation of the brain dopamine system may mediate cocaine reward, craving and relapse [2]. One approach to treating this dysregulation has been the use of medications that increase dopamine activity. Selegiline, a relatively selective monoamine oxidase (MAO)-B inhibitor at lower doses has been investigated as a pharmacological treatment for cocaine dependence.Selegiline, approved for the treatment of Parkinson's Disease, inactivates MAO-B irreversibly and increases its substrate dopamine in the synapse; reactivation requires at least
%U http://www.biomedcentral.com/1472-6904/9/13