Safety of Abt-724On May 31, 2008, Newman-Tancredi, Adrian; Heusler, Peter; Martel, Jean-Claude; Ormiere, Anne-Marie; Leduc, Nathalie; Cussac, Didier published an article in International Journal of Neuropsychopharmacology. The article was 《Agonist and antagonist properties of antipsychotics at human dopamine D4.4 receptors: G-protein activation and K+ channel modulation in transfected cells》. The article mentions the following:
Interaction at dopamine D4 receptors may improve cognitive function, which is highly impaired in individuals with schizophrenia, but comparative studies of recent antipsychotics in cellular models of D4 receptor activation are lacking. Here, we report the in-vitro profile of over 30 ligands at recombinant hD4.4 receptors. In [35S]GTPγS binding experiments using membranes of CHO-hD4.4 cells, apomorphine, preclamol and the selective D4 agonists, ABT724, CP226269, Ro-10-5824 and PD168077, behaved as partial agonists (Emax 20-60% vs. dopamine), whereas L745870 and RBI257, displayed antagonist properties. The conventional’ antipsychotic, haloperidol and the atypicals’, clozapine and risperidone, exhibited antagonist properties, while third generation’ compounds bifeprunox, SLV313 and F15063, acted as partial agonists (10-30%). Aripiprazole and SSR181507 slightly stimulated [35S]GTPγS binding at micromolar concentrations In Xenopus laevis oocytes co-expressing hD4.4 receptors with G-protein-coupled inwardly rectifying potassium (GIRK) channels, apomorphine, preclamol, ABT724, CP226269, and PD168077 stimulated GIRK currents (Emax 70-80%). The 5-HT1A receptor ligands, WAY100635 and flibanserin, also exhibited partial agonist activity (30% and 15%, resp.). Haloperidol, clozapine, olanzapine and nemonapride did not stimulate GIRK currents, whereas aripiprazole, bifeprunox, SLV313 and F15063, but not SSR181507, exhibited partial agonism (Emax 20-35%). In-vitro responses depended on exptl. conditions: increasing NaCl concentration (30 mm to 100 mm) reduced agonist efficacy in [35S]GTPγS binding, whereas decreasing the amount of hD4.4 cRNA injected into oocytes (from 2.0 to 0.5 ng/oocyte) reduced agonist efficacy of several compounds These data indicate that, unlike conventional or atypical’ antipsychotics, several third generation’ agents display D4 receptor partial agonism that may be sufficient to influence physiol. D4 receptor activity in vivo. In the experiment, the researchers used many compounds, for example, Abt-724(cas: 70006-24-5Safety of Abt-724)
Abt-724(cas: 70006-24-5) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Safety of Abt-724
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics