Monoamine transporter inhibitors and substrates as treatments for stimulant abuse.
The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters, in general, and dopamine transporters, in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination, and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use.
Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA. Electronic address: lhowell@emory.edu.
Leonard L
LL
Howell
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
S Stevens
SS
Negus
D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000697:Central Nervous System Stimulants; D026901:Membrane Transport Proteins; D009025:Morpholines; D050493:Vesicular Monoamine Transport Proteins; D015283:Citalopram; C100294:phendimetrazine
Amphetamine; Cocaine; Dopamine; Drug discrimination; Monoamines; Neuroimaging; Nonhuman primates; Norepinephrine; Self-administration; Serotonin