title: Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals: Implications for Agonist-like Replacement Therapy.
abstract: Phendimetrazine is a prodrug for the monoamine releaser phenmetrazine-a drug with known abuse potential. Preclinical studies suggest that phendimetrazine has limited abuse potential and may have promise as an agonist-like replacement therapy for cocaine dependence. This study evaluated the abuse potential of phendimetrazine in humans.
  
  
  
  Nine cocaine-dependent individuals (N = 9) were enrolled to investigate the abuse potential of phendimetrazine and d-amphetamine, using a double-blind, placebo-controlled, within-subject design. Subjective and cardiovascular effects of oral phendimetrazine (35, 70, and 105 mg), d-amphetamine (10, 20, and 30 mg), and placebo were assessed in quasi-random order across 8 sessions lasting for approximately 8 hours each.
  
  
  
  d-Amphetamine (20 and 30 mg) significantly increased cardiovascular measures in a time and dose-related manner, but phendimetrazine did not systematically alter cardiovascular measures. Although d-amphetamine and phendimetrazine significantly increased ratings indicative of abuse potential (eg, drug liking) and stimulant-like effects relative to placebo, these increases were generally small in magnitude, with phendimetrazine producing significant effects on fewer abuse-related measures and at fewer time points than d-amphetamine.
  
  
  
  These preliminary findings suggest that oral phendimetrazine and d-amphetamine may have limited abuse potential in cocaine-dependent individuals. These findings collectively emphasize that the clinical utility of medications to treat cocaine-use disorders should be weighed carefully against their potential for abuse and diversion, with careful attention paid to evaluating abuse potential in a clinically relevant population of interest. Future studies are needed to further elucidate the potential utility of phendimetrazine as an agonist-like replacement therapy for cocaine dependence.
authors.affiliation: Department of Behavioral Science (BLB, WWS, CRR), University of Kentucky College of Medicine, 140 Medical Behavioral Science Building, Lexington, KY; Department of Psychology (WWS, CRR), University of Kentucky College of Arts and Sciences, 110 Kastle Hall, Lexington, KY; Department of Psychiatry (WWS, CRR), University of Kentucky College of Medicine, 3470 Blazer Parkway, Lexington, KY; and University of Kentucky College of Medicine (JPS), 138 Leader Avenue, Lexington, KY.
authors.forename: B Levi
authors.initials: BL
authors.lastname: Bolin
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Sites
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
mesh_terms: D000328:Adult; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects*; D063487:Prescription Drug Misuse; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D009025:Morpholines; C100294:phendimetrazine; D003913:Dextroamphetamine