Tiospirone

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.

Ziprasidone, a benzisothiazolyl piperazine derivative of tiospirone, is a second-generation antipsychotic with high-affinity antagonism for 5-hydroxytryptophan (5HT)(2A), 5HT(2C), 5HT(1D) and D(2) receptors, pre- and post-synaptic agonism for 5HT(1A) receptors, and inhibition of reuptake for serotonin and norepinephrine. Initially approved for the treatment of adults with schizophrenia, ziprasidone has more recently received supplementary indications for acute manic and mixed episodes and as maintenance therapy for people affected by bipolar disorder. Based on MEDLINE citations up to November 2010 and hand-searched references, this article relating to ziprasidone addresses its short- and long-term efficacy and safety, according to the results of randomized clinical trials, open-label studies and real-world experiences. Emerging evidence indicates that in patients with bipolar disorder, ziprasidone provides valid efficacy and remarkable safety when administered alone for the treatment of manic and mixed episodes. The same applies when ziprasidone is administered in combination with lithium or valproate for the prevention of affective relapses and recurrences. Any conclusion on the potential of ziprasidone as an antidepressant should be postponed because of insufficient evidence.