title: A phase 1 trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion.
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.
  
  
  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.
authors: Department of Psychiatry, University of Cincinnati, OH, USA. debra.harris4@va.gov
authors: Debra S
authors: DS
authors: Harris
authors: Thomas
authors: T
authors: Everhart
authors: Peyton
authors: P
authors: Jacob
authors: Emil
authors: E
authors: Lin
authors: John E
authors: JE
authors: Mendelson
authors: Reese T
authors: RT
authors: Jones
mesh_terms: 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
chemical_list: 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