title: Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. mbanks7@vcu.edu
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Banks
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Blough
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage*; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001067:Appetite Depressants; D000697:Central Nervous System Stimulants; D009025:Morpholines; C100294:phendimetrazine; D003042:Cocaine
keywords: Amphetamine; Choice; Cocaine; Phendimetrazine; Phenmetrazine; Rhesus monkey