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


CONCLUSIONS
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.
Harris
Debra S
DS
Department of Psychiatry, University of Cincinnati, OH, USA. debra.harris4@va.gov
Everhart
Thomas
T
Jacob
Peyton
P
Lin
Emil
E
Mendelson
John E
JE
Jones
Reese T
RT
D000279:Administration, Cutaneous; D000328:Adult; D000339:Affect / Q000187:drug effects; D000661:Amphetamine / Q000378:metabolism; D000662:Amphetamines / Q000378:metabolism; D000704:Analysis of Variance; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006719:Homovanillic Acid / Q000097:blood / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008694:Methamphetamine / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D008991:Monitoring, Physiologic; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010627:Phenethylamines / Q000378:metabolism / Q000652:urine; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D012642:Selegiline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D055815:Young Adult
D000662:Amphetamines; D018765:Dopamine Uptake Inhibitors; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; C030284:3-methoxy-4-hydroxyphenylglycol sulfate; D012642:Selegiline; C029261:phenethylamine; D008694:Methamphetamine; D008734:Methoxyhydroxyphenylglycol; C005618:benzoylecgonine; C017861:desmethylselegiline; D011388:Prolactin; D000661:Amphetamine; D008995:Monoamine Oxidase; D003042:Cocaine; D006719:Homovanillic Acid