Cited by 68Neurotransmitter Receptor Influence on BehaviorReceptor Mechanisms and SignalingNeuroscience and Neuropharmacology Research

The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT1A receptor

Markowitz, J. S., Markowitz, J. S., DeVane, C. L., Ramamoorthy, S., Zhu, Hao-Jie, Zhu, Hao-Jie·2009·Die Pharmazie

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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Crossref · 10.31083/ph.2009.8691

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Authors
Markowitz, J. S., Markowitz, J. S., DeVane, C. L., Ramamoorthy, S., Zhu, H.-J., & Zhu, H.-J.
Affiliations
Medical University of South Carolina (US)
Venue
Die Pharmazie
Publisher
IMR Press
Published
2009-02-01
Volume
64
Issue
2
Pages
123-5
ISSN
  • 0031-7144 (ISSN-L)
  • 3053-691X
OpenAlex
W56688777
Cited by
68
References
13
Citations by year
2025: 11 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 26 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2012: 1
FWCI
0.28
Type
journal article
Language
en
Open access
closed
Locations
  • Die Pharmazie (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
5-HT1A receptor, 5-HT2B receptor, psychostimulants, dopamine release, guinea pig ileum, 8-OH-DPAT, GTPgammaS binding
MeSH terms
Central Nervous System Stimulants, Animals, Cricetulus, Female, Guinea Pigs, Cricetinae, Ileum, Male, Methylphenidate, Guanosine 5'-O-(3-Thiotriphosphate), CHO Cells, Rats, Wistar, Serotonin Receptor Agonists, Receptor, Serotonin, 5-HT1A, Receptor, Serotonin, 5-HT2B, Rats, Serotonin 5-HT1 Receptor Agonists, Serotonin 5-HT2 Receptor Agonists, In Vitro Techniques

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