Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys

Drug Alcohol Depend. 2013 Aug 1;131(3):204-13. doi: 10.1016/j.drugalcdep.2013.05.005. Epub 2013 May 31.

Abstract

Background: The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4).

Methods: Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1mg/kg/h; N=6) were also examined for comparison.

Results: During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects.

Conclusions: These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability.

Keywords: Amphetamine; Choice; Cocaine; Phendimetrazine; Phenmetrazine; Rhesus monkey.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Appetite Depressants / administration & dosage*
  • Behavior, Addictive / drug therapy*
  • Behavior, Addictive / psychology
  • Central Nervous System Stimulants / administration & dosage
  • Choice Behavior / drug effects*
  • Choice Behavior / physiology
  • Cocaine / administration & dosage*
  • Feeding Behavior / drug effects*
  • Feeding Behavior / physiology
  • Feeding Behavior / psychology
  • Infusions, Intravenous
  • Macaca mulatta
  • Male
  • Morpholines / administration & dosage*
  • Time Factors
  • Treatment Outcome

Substances

  • Appetite Depressants
  • Central Nervous System Stimulants
  • Morpholines
  • phendimetrazine
  • Cocaine