NeuroAct Communication offers expert guidance to scientific communication.

  • Define a publication strategy: identify objectives, target audience, journals
  • Aid to effective presentation of pharmacological data
  • Experienced scientific writing and editing: research reports, posters, symposia

For more information Contact.


Stimulation by antipsychotic agents of mitogen-activated protein kinase (MAPK) coupled to cloned, human (h)serotonin 5-HT1A receptors.

Cussac D, Duqueyroix D, Newman-Tancredi A, Millan MJ.
Psychopharmacology (Berl). 2002 Jul;162(2):168-77. Epub 2002 Apr 30.

RATIONALE: There is evidence that serotonergic mechanisms contribute to the functional profiles of antipsychotic drugs, several of which display affinity for human (h)5-HT1A receptors. OBJECTIVE: Here, we compared the interaction of several antipsychotic agents at h5-HT1A receptors employing mitogen-activated protein kinase (MAPK), an intracellular marker. METHODS: The influence of antipsychotics on MAPK phosphorylation was quantified in Chinese hamster ovary (CHO) cells stably transfected with h5-HT1A receptors by use of a highly selective antibody. RESULTS: The novel antipsychotic agent, S16924, concentration-dependently (pEC50, 8.10) stimulated the phosphorylation of MAPK. Its maximal effect (96%) was similar to that of the prototypical 5-HT1A agonist, (+)8-OH-DPAT (pEC50, 8.54) (defined as 100%). The selective 5-HT1A receptor antagonist WAY100,635, which was inactive alone, abolished stimulation of MAPK by S16924 with a pK(b) of 9.66. This stimulatory influence of S16924 on MAPK was potently mimicked by the benzoisoxazole, antipsychotic ziprasidone (pEC50, 7.25; 93%). The atypical antipsychotic clozapine also activated MAPK, albeit with lower potency and efficacy (pEC50, 5.43 and 43%). These actions of ziprasidone and clozapine were also blocked by WAY100,635. Evaluated at a single, high concentration, several other antipsychotics stimulated MAPK phosphorylation with variable efficacy: quetiapine (75%), ocaperidone (74%), tiospirone (57%), olanzapine (54%) and risperidone (21%). In all cases, their actions were abolished by WAY100,635. In contrast, haloperidol, thioridazine and sertindole did not stimulate MAPK. CONCLUSIONS: Antipsychotics display contrasting efficacies in modulating MAPK phosphorylation at h5-HT1A receptors, ranging from high (e.g. S16924 and ziprasidone), via intermediate (e.g. clozapine) to low (e.g. haloperidol). Differential modulation of 5-HT1A receptor-coupled MAPK may contribute to their contrasting functional profiles.