Effects of Daily Oral Phendimetrazine on Cocaine‐Food Choice in Rhesus Monkeys

Current treatments for cocaine abuse have not been efficacious in the majority of patients. One strategy examined in these studies is for pharmacotherapies to involve combination treatments in which one drug is a long‐acting “agonist” and a second drug administered in combination to perhaps enhance the effects of both drugs. Phendimetrazine is a clinically available anorectic agent that is a prodrug to phenmetrazine, an amphetamine‐like compound, and may have lower abuse liability in comparison to other agonist therapies. Research has shown phendimetrazine reduced cocaine choice by rhesus monkeys when given intravenously by continuous infusion (Banks et al., 2013). The present study examined the effects of oral phendimetrazine on cocaine choice in rhesus monkeys; this treatment route may better represent how the drug would be administered clinically. In this study, rhesus macaques (n=4) were trained to choose between banana‐flavored pellets and cocaine doses (0, 0.003–0.1 mg/kg/injection). Complete cocaine dose‐response curves were determined each session and cocaine choice increased as a function of cocaine dose. Once the monkeys' responding was stable, they were given phendimetrazine orally twice a day and tested once a week on the choice procedure. The dose of phendimetrazine always started at 4.0 mg/kg and increased depending on whether the monkey's choice changed. If the phendimetrazine dose lowered cocaine choice, the monkey would continue on this dose for another week. However, if cocaine choice remained at baseline or increased the dose of phendimetrazine would increase. Blood samples were taken weekly to ensure that the monkeys were taking the oral phendimetrazine. In preliminary findings, oral (6.0 mg/kg) phendimetrazine initially decreased cocaine choice in two monkeys, but tolerance developed to this effect. At present, it is unclear why these results vary from Banks et al. (2013), but could be due to a number of reasons such as the route and duration of administration of phendimetrazine or the availability of cocaine in which monkeys in the present study were tested weekly rather than daily in the Banks et al. study. Measures of plasma phendimetrazine and phenmetrazine will provide important information. Future directions include examining these methodological issues and to add a second drug to extend the initial effects of phendimetrazine in lowering cocaine choice. Support or Funding Information DA06634