Tiospirone

Schizophrenia is a chronic neurol. disorder in which a person suffers from emotional and intellectual disturbances.First generation antipsychotics for Schizophrenia were replaced with by second generation ones with less side-effects like Parkinsonism and Hyperprolactinemia.A novel, computer-based drug designing technique, has emerged to develop more efficient drugs.One of the computational methods becoming increasingly popular to develop new drugs is relying on Pharmacophores.This method was utilized to develop pharmacophore models of Akt2 inhibitors and β2-Adrenoceptor agonists.A pharmacophore model is proposed, using fourteen second generation and one first generation antipsychotic drugs for Schizophrenia that are effective against both 5-HT2a and D2 receptors.Hydrogen bond acceptors (I1BA), aromatic rings (AR ring) and pos. ionizable (PI) groups were identified computationally as pharmacophore features by LigandScout.The distance range calculated by Visual Mol. Dynamics (VMD) between AR-HBA, AR-PI and HBA- PI was 3.68 A°-5.74 A°, 5.66 A°-7.64 A° and 3.77 A°-5.38 A°, resp.This study should help finding specific and more efficient drugs for Schizophrenia in future.

Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury.