Dopamine D1 and D2 receptors mediate opposite functions in seizures induced by lithium-pilocarpine.

The effect of selective dopamine receptor blockade on epileptic activity was tested in rats. using the lithium-pilocarpine seizure model. One day after lithium pretreatment, systemic administration of the dopamine D1antagonist, SCH 23390, prevented the convulsive activity induced by either 10 or 15 mg/kg of pilocarpine in a dose-dependent manner as revealed by behavioral and electroencephalographic alterations. No anticonvulsant effect was observed when SCH 23390 was injected at the same time as lithium and 24 h prior to pilocarpine. Furthermore, the D2antagonists, raclopride and haloperidol, potently reduced the threshold for convulsions induced by 10 mg/kg of pilocarpine, following lithium pretreatment. Neither dopamine D1nor D2, antagonists altered the limbic stereotypies induced by pilocarpine, supporting the view that the dopamine system is primarily involved in the mechanisms of convulsion generation and seizure spreading. These results indicate that dopamine receptor subtypes exert opposite functions on the regulation of convulsive activity. © 1991

Cariprazine (RGH-188). A new pharmacological target option for the treatment of schizophrenia, bipolar disorders and depression?

Ntroduction: Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Its interesting pharmacodynamic profile suggests its potential in the treatment of a plethora of psychiatric disorders. The present comprehensive review aims at summarizing the current evidence about the safety, tolerability and efficacy of Cariprazine in the treatment of schizophrenia, BD (manic/mixed/depressive episode) and MDD. EVIDENCEACQUISITION: Aliterature search was here carried out on PubMed/Medline/Scopus and the database on Clinical Trials from inception until December 2015 by typing a set of specified keywords. EVIDENCE SYNTHESIS: Cariprazine appears to be efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. CONCLUSIONS: Further studies should be needed in order to better identify its clinical efficacy profile