The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor.

Article Details

Citation

Markowitz JS, DeVane CL, Ramamoorthy S, Zhu HJ

The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor.

Pharmazie. 2009 Feb;64(2):123-5.

PubMed ID
19322953 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Methylphenidate5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Not AvailableDetails
Serdexmethylphenidate5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Agonist
Details