Reduced cardiovascular effects of methamphetamine following treatment with selegiline.
Selegiline is a specific MAO-B inhibitor. As MAO-B has been shown to be significantly involved in the metabolism of dopamine in certain regions of the primate brain, selegiline has been proposed for use in the treatment of drug addiction. Selegiline is also metabolized in vivo to l-methamphetamine. Therefore, when given in combination with psychostimulants such as d-methamphetamine, there is the potential for adverse effects. To study this possibility, squirrel monkeys were treated with chronic selegiline and tested with two doses of d-methamphetamine (0.1 and 1.0 mg/kg, i.v.). Following at least 7 days of treatment with once daily 0.3 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were no different than the effects of methamphetamine observed prior to selegiline treatment. However, following at least 10 days of treatment with 1.0 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were significantly reduced. Both methamphetamine and amphetamine were detected in plasma following chronic selegiline treatment. When monkeys were given an acute selegiline injection prior to methamphetamine, reduced cardiovascular effects were also seen. These results indicate that selegiline can be used safely even in combination with methamphetamine, as the cardiovascular effects of the drug combination were no greater than either drug alone, and were actually reduced at the higher selegiline dose.
Schindler
Charles W
CW
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, DHHS/NIH/NIDA Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. cshindl@helix.nih.gov
Gilman
Joanne P
JP
Graczyk
Zofi
Z
Wang
Ganfeng
G
Gee
Winnie L
WL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004361:Drug Tolerance; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012453:Saimiri; D012642:Selegiline / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008694:Methamphetamine