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Updated: Jun 24, 2026

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology
Published on: March 27, 2018
The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor
J S Markowitz1, C L DeVane, S Ramamoorthy
1Laboratory of Drug Disposition and Pharmacogenetics, Department of Pharmaceutical and Biomedical Sciences, Charles P. Darby Children's Research Institute, RM 412, Medical University of South Carolina, Charleston, SC 29425, USA. markowij@musc.edu
Abstract:
The present study was undertaken to determine whether d-threo-(R,R)-methylphenidate (MPH) was exerting binding activity as an agonist or antagonist of 5-HT1A and 5-HT2B receptors. [35S]guanosine5'[gamma-thio]triphosphate ([35S]GTPgammaS) binding assay and field-stimulated Guinea pig ileum assay were used to determine 5-HT(1A) receptor agonism and antagonism activity of d-threo-(R,R)-MPH. The results suggested d-threo-(R,R)-MPH induced 5-HT(1A) receptor agonist activity at 100 microM. The Guinea pig ileum functional assay showed that d-threo-(R,R)-MPH produced agonist-like reduction of neurogenic twitch with an EC50 5.65 +/- 0.36 microM. At 30 microM concentrations, d-threo-(R,R)-MPH produced 171 +/- 4.24% of the relaxation relative to that caused by 0.12 microM 8-OH-DPAT. However, d-threo-(R,R)-MPH exhibited no significant pharmacological activity in rat stomach fundus 5-HT(2B) receptor functional assay. Thus, d-threo-(R,R)-MPH appears to act as a selective 5-HT(1A) receptor agonist in vitro. It is speculated that the activation of 5-HT(1A) receptor might play a partial role in d-threo-(R,R)-MPH mediated dopamine (DA) release in the brain.
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