In vitro and in vivo characterization of F-97013-GD, a partial 5-HT1A agonist with antipsychotic- and antiparkinsonian-like properties

Neuropharmacology
Arturo ZazpeAurelio Orjales

Abstract

In order to better define the role of 5-HT(1A) receptors in the modulation of extrapyramidal motor functions, we investigated the effect of 5-HT(1A) agonists on tacrine-induced tremulous jaw movements (TJM) in rats, a putative model of parkinsonian tremor. Acute injection of 5-HT(1A) agonists 8-OH-DPAT and buspirone dose-dependently counteracted the tacrine-induced oral movements (ED(50)=0.04 and 1.0mg/kg, respectively), an effect reversed by the selective 5-HT(1A) antagonist WAY 100,635. In contrast to classical antipsychotics, the atypical antipsychotics risperidone (ED(50)=0.3mg/kg) and clozapine (ED(50)=1.5mg/kg) blocked the oral movements induced by the cholinomimetic agent at or below the doses required for suppression of conditioned avoidance response. The compound F-97013-GD (6-methyl-2-[4-(naphtylpiperazin-1-yl)butyl]-3-(2H)-pyridazinone), a putative antipsychotic drug that in functional in vitro and in vivo assays behaved as a mixed dopamine D(2)-antagonist and 5-HT(1A)-partial agonist, also displayed a potent antitremorgenic effect in this paradigm (ED(50)=0.5mg/kg). Interestingly, pretreatment with WAY 100,635 blocked the inhibitory effect of F-97013-GD but not that of clozapine. The 5-HT depleting agent para-chloro...Continue Reading

References

Dec 1, 1991·British Journal of Pharmacology·M OshitaI Muramatsu
Mar 30, 2001·Journal of Psychopharmacology·R A BantickP M Grasby
Dec 14, 2002·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Siegfried KasperThomas Brücke
Feb 26, 2003·Neurology·M DoderUNKNOWN 11C-WAY 100635 PET study

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Citations

Apr 18, 2014·Indian Journal of Pharmacology·Jayasankar KosarajuM N Satish Kumar
May 29, 2010·Pharmacological Reports : PR·Alireza M NayebiMorteza Samini
Apr 20, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Saki ShimizuYukihiro Ohno
May 23, 2008·Progress in Neuro-psychopharmacology & Biological Psychiatry·Yukihiro OhnoYoshiko Kawai
Jul 11, 2013·Progress in Neuro-psychopharmacology & Biological Psychiatry·Saki ShimizuYukihiro Ohno
Apr 6, 2021·The European Journal of Neuroscience·Isabelle WakuAmanda R de Oliveira

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