Research article summary (published 30 Jul 2009):

A phase 1 trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion.

Full 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.

Author information

Author/s: Harris, Debra S (DS); Everhart, Thomas (T); Jacob, Peyton (P); Lin, Emil (E); Mendelson, John E (JE); Jones, Reese T (RT);

Affiliation: Department of Psychiatry, University of Cincinnati, OH, USA. debra.harris4(-atsign-)va.gov

Grants: N01 DA-0-8807 (Agency:NIDA NIH HHS) ; RR-00079 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural

Journal: BMC clinical pharmacology (BMC Clin Pharmacol), published in England. (Language: eng)

Reference: 2009-; vol 9 (issue ) : pp 13

Dates: Created 2009/08/24; Completed 2009/09/16;

PMID: 19646280, status: MEDLINE (last retrieval date: 9/16/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Administration, Cutaneous Adult Affect - drug effects Amphetamine - metabolism Amphetamines - metabolism Analysis of Variance Cocaine - administration & dosage; analogs & derivatives; metabolism; pharmacokinetics; pharmacology; toxicity Dopamine Uptake Inhibitors - pharmacokinetics; pharmacology; toxicity Drug Interactions - physiology Female Homovanillic Acid - blood; metabolism Humans Infusions, Intravenous

Infusions, Intravenous Male Methamphetamine - metabolism Methoxyhydroxyphenylglycol - analogs & derivatives; metabolism; urine Monitoring, Physiologic Monoamine Oxidase - metabolism Monoamine Oxidase Inhibitors - administration & dosage; pharmacokinetics; pharmacology Phenethylamines - metabolism; urine Prolactin - blood; metabolism Selegiline - administration & dosage; pharmacokinetics; pharmacology Statistics, Nonparametric Substance Withdrawal Syndrome - psychology Young Adult

Associated Chemicals: Amphetamines (0) ; Dopamine Uptake Inhibitors (0) ; Monoamine Oxidase Inhibitors (0) ; Phenethylamines (0) ; Selegiline (14611-51-9) ; desmethylselegiline (18913-84-3) ; 3-methoxy-4-hydroxyphenylglycol sulfate (28700-49-4) ; Amphetamine (300-62-9) ; Homovanillic Acid (306-08-1) ; Cocaine (50-36-2) ; benzoylecgonine (519-09-5) ; Methoxyhydroxyphenylglycol (534-82-7) ; Methamphetamine (537-46-2) ; phenethylamine (64-04-0) ; Prolactin (9002-62-4) ; Monoamine Oxidase (EC 1.4.3.4)

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