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Inverse Agonist Properties of Antipsychotic Agents at Cloned, Human (h) Serotonin (5-HT)1B and h5-HT1D Receptors
- Source :
- Neuropsychopharmacology. 25:410-422
- Publication Year :
- 2001
- Publisher :
- Springer Science and Business Media LLC, 2001.
-
Abstract
- The actions of diverse antipsychotics at cloned h5-HT(1B) and h5-HT(1D) receptors were examined employing [3H]-GR125,743 and [35S]-GTPgammaS for determination of affinities and efficacies, respectively. Compared with hD(2) receptors, haloperidol, chlorpromazine and olanzapine showed markedly (100-fold) lower affinity for h5-HT(1D) and h5-HT(1B) receptors at which they expressed inverse agonist properties. Clozapine, risperidone and ocaperidone likewise behaved as inverse agonists at h5-HT(1B) and h5-HT(1D) receptors but their affinities were only approximately 10-fold lower than at hD(2) receptors. Moreover, ziprasidone, S16924 and ORG5222 interacted at h5-HT(1B) and h5-HT(1D) receptors with affinities similar to hD(2) sites. While S16924 and ORG5222 were inverse agonists at h5-HT(1B) and h5-HT(1D) sites, ziprasidone was an inverse agonist at h5-HT(1D) receptors yet a partial agonist at h5-HT(1B) receptors. These actions of antipsychotics were abolished by the selective, neutral antagonist, S18127. In conclusion, with the exception of ziprasidone, all antipsychotics were inverse agonists at h5-HT(1B) and h5-HT(1D) receptors, although they differed markedly in their potency at these sites as compared to hD(2) receptors.
- Subjects :
- medicine.medical_specialty
Guinea Pigs
CHO Cells
Pharmacology
Partial agonist
Cricetinae
Internal medicine
medicine
Animals
Inverse agonist
Ziprasidone
Cloning, Molecular
Chlorpromazine
Receptor
5-HT receptor
Receptors, Dopamine D2
Chemistry
Recombinant Proteins
Rats
Serotonin Receptor Agonists
Psychiatry and Mental health
Endocrinology
Guanosine 5'-O-(3-Thiotriphosphate)
Receptor, Serotonin, 5-HT1D
Receptors, Serotonin
Receptor, Serotonin, 5-HT1B
Serotonin
Endogenous agonist
Antipsychotic Agents
medicine.drug
Subjects
Details
- ISSN :
- 0893133X
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....d6289c148a42165a267ee8832b0405f7