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Tight binding dopamine reuptake inhibitors as cocaine antagonists

Year: 1989

Type: article

Abstract: The experiments reported in this study tested the hypothesis that tight binding dopamine (DA) reuptake inhibitors might act as cocaine antagonists. Binding studies demonstrated that the high affinity dopamine reuptake inhibitor, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine (GBR12909) produced a wash-resistant inhibition of the DA transporter in rat striatal membranes as labeled by [3H]cocaine or [3H]1-[2-(diphenyl- methoxy)ethyl]-4-(3-phenylpropyl)piperazine [( 3H]GBR12935), indicative of tight binding. In vivo microdialysis experiments showed that administration of 25 mg/kg GBR12909 to rats produced a modest, but not statistically significant, increase in the extracellular levels of striatal DA, while this same dose of GBR12909 inhibited the ability of cocaine to elevate extracellular DA levels by 64%. These data suggest that tight binding DA reuptake blockers may provide a fruitful approach for developing a cocaine antagonist.

Source: FEBS Letters

DOI: 10.1016/0014-5793(89)81566-2

Authors: Richard B. Rothman, Andrea Mele, Audrey A. Reid, Hyacinth Akunne, Nigel Greig, Andrew Thurkauf, Kenner C. Rice, Agu Pert

Institutions: National Institutes of Health, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases

Language: English

Topic: Neurotransmitter Receptor Influence on Behavior

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W1537128490

FWCI: 1.068

Cites: 24

Cited by: 61

Related to: 10