Neuropharmacological Profile of an Atypical Antipsychotic, NRA0562

Abstract

Schizophrenia is a serious and disabling psychiatric disorder affecting approximately 1% of the world's population. A new generation of atypical antipsychotics has been introduced over the past decade. These atypical antipsychotics have comparable or greater efficacy than traditional antipsychotics in the treatment of the psychotic symptoms of schizophrenia and a much improved neurologic side effect profile. This paper reviews the pharmacological efficacy and safety of a potential atypical antipsychotic, NRA0562.NRA0562 has a high affinity for dopamine D 1 , D 2L , D 4.2 , 5-HT 2A receptors as well as á 1 -adrenoceptors, and has a moderate affinity for H 1 receptors. NRA0562 strongly binds to 5-HT 2A receptors and á 1 -adrenoceptors in the frontal cortex, its binding to striatal D 2 receptors is weaker, similar to that of clozapine.NRA562 displayed potent antipsychotic activities in animal models of schizophrenia, such as methamphetamine (MAP)-induced hyperactivity, apomorphine-induced disruption of pre-pulse inhibition and conditioned avoidance test. NRA0562 is more potent in reversing the inhibitory effects of MAP at A10 than at A9 dopamine neurons. It increased Fos-like immunoreactivity in the nucleus accumbens more effectively than in the dorsolateral striatum, indicating that NRA0562 has the profile of an atypical antipsychotic. In vivo assays for extrapyramidal side effect liability showed that NRA0562 has a low rate of neurological side effects. Thus, NRA0562 may have unique antipsychotic activity with a lower propensity for extrapyramidal side effects.

One-pot and multi-step syntheses of new 2-(4,5-dihydro-1H-pyrazol-1-yl) thiazole derivatives

“…Among heterocyclic compounds, pyrazole and thiazole scaffolds are very popular because of their versatility in use. The pyrazole derivatives possess an extensive range of biological activities such as anxiolytic 4 , antimicrobial 5 , antihypertensive 6 , antiinflammatory 7 , antipyretic 8 , analgesic 9 , antioxidant 10 , anticancer 11 , sodium channel blocker 12 , antiviral 13 , antidepressant 14 and antidiabetic activity 15 , while the thiazole derivatives which is found in the structure of many compounds naturally found in nature have antiinflammatory 16 , antibacterial 17 , antifungal 18 , antithrombotic 19 , antiHIV 20 , antihypertensive 21 , hypnotic 22 , analgesic 23 , neuroleptic 24 , and antimalarial effects 25 . Also, pyrazole and thiazole compounds having a five atomic ring structure are used in the synthesis of many condensed hetero structures.…”