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

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  • Author(s): Harris DS;Harris DS; Everhart T; Jacob P 3rd; Lin E; Mendelson JE; Jones RT
  • Source:
    BMC clinical pharmacology [BMC Clin Pharmacol] 2009 Aug 01; Vol. 9, pp. 13. Date of Electronic Publication: 2009 Aug 01.
  • Publication Type:
    Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101088667 Publication Model: Electronic Cited Medium: Internet ISSN: 1472-6904 (Electronic) Linking ISSN: 14726904 NLM ISO Abbreviation: BMC Clin Pharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      Cocaine/*pharmacology ; Dopamine Uptake Inhibitors/*pharmacology ; Monoamine Oxidase Inhibitors/*pharmacology ; Selegiline/*pharmacology; Administration, Cutaneous ; Adult ; Affect/drug effects ; Amphetamine/metabolism ; Amphetamines/metabolism ; Analysis of Variance ; Cocaine/administration & dosage ; Cocaine/analogs & derivatives ; Cocaine/metabolism ; Cocaine/pharmacokinetics ; Cocaine/toxicity ; Dopamine Uptake Inhibitors/pharmacokinetics ; Dopamine Uptake Inhibitors/toxicity ; Drug Interactions/physiology ; Female ; Homovanillic Acid/blood ; Homovanillic Acid/metabolism ; Humans ; Infusions, Intravenous ; Male ; Methamphetamine/metabolism ; Methoxyhydroxyphenylglycol/analogs & derivatives ; Methoxyhydroxyphenylglycol/metabolism ; Methoxyhydroxyphenylglycol/urine ; Monitoring, Physiologic ; Monoamine Oxidase/metabolism ; Monoamine Oxidase Inhibitors/administration & dosage ; Monoamine Oxidase Inhibitors/pharmacokinetics ; Phenethylamines/metabolism ; Phenethylamines/urine ; Prolactin/blood ; Prolactin/metabolism ; Selegiline/administration & dosage ; Selegiline/pharmacokinetics ; Statistics, Nonparametric ; Substance Withdrawal Syndrome/psychology ; Young Adult
    • 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.
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    • Grant Information:
      M01 RR000079 United States RR NCRR NIH HHS; N01 DA-0-8807 United States DA NIDA NIH HHS; RR-00079 United States RR NCRR NIH HHS
    • Accession Number:
      0 (Amphetamines)
      0 (Dopamine Uptake Inhibitors)
      0 (Monoamine Oxidase Inhibitors)
      0 (Phenethylamines)
      28700-49-4 (3-methoxy-4-hydroxyphenylglycol sulfate)
      2K1V7GP655 (Selegiline)
      327C7L2BXQ (phenethylamine)
      44RAL3456C (Methamphetamine)
      534-82-7 (Methoxyhydroxyphenylglycol)
      5353I8I6YS (benzoylecgonine)
      5F44WR1I53 (desmethylselegiline)
      9002-62-4 (Prolactin)
      CK833KGX7E (Amphetamine)
      EC 1.4.3.4 (Monoamine Oxidase)
      I5Y540LHVR (Cocaine)
      X77S6GMS36 (Homovanillic Acid)
    • Publication Date:
      Date Created: 20090804 Date Completed: 20090916 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      PMC2731040
    • Accession Number:
      10.1186/1472-6904-9-13
    • Accession Number:
      19646280