Contemporary society is characterized by rapid changes. Various epidemiological, political and economic crises represent a burden to mental health of nowadays population, which may at least partially explain the increasing incidence of mental disorders, including schizophrenia. Schizophrenia is associated with premature mortality by at least 13-15 years. The leading cause of premature mortality in schizophrenia patients is high incidence of cardiovascular diseases. The specific-cause mortality risk for cardiovascular diseases in schizophrenia patients is more than twice higher as compared to the general population. Several factors are discussed as the factor of cardiovascular diseases development. Intensive efforts to identify possible link between schizophrenia and cardiovascular diseases are made. It seems that sigma 1 receptor may represent such link. By modulation of the activity of several neurotransmitter systems, including dopamine, glutamate, and GABA, sigma 1 receptor might play a role in pathophysiology of schizophrenia. Moreover, significant roles of sigma 1 receptor in cardiovascular system have been repeatedly reported. The detailed role of sigma 1 receptor in both schizophrenia and cardiovascular disorders development however remains unclear. The article presents an overview of current knowledge about the association between schizophrenia and cardiovascular diseases and proposes possible explanations with special emphasis on the role of the sigma 1 receptor.

• MeSH
• Cardiovascular Diseases * diagnosis   epidemiology   MeSH
• Cardiovascular System * MeSH
• Humans MeSH
• Schizophrenia * diagnosis   epidemiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Antipsychotic drug perphenazine belongs to the phenothiazine group commonly reported to induce ECG changes and tachyarrhythmias. Data about its effect on ionic membrane currents in cardiomyocytes are missing. We analyzed the effect of perphenazine (0.1-100 microM) on fast sodium current I (Na) and transient outward potassium current I (to) in enzymatically isolated rat right ventricular myocytes by the whole-cell patch-clamp technique at room temperature. Perphenazine reversibly blocked I (Na) (reducing its amplitude; IC(50) = 1.24 +/- 0.10 microM) and I (to) (accelerating its apparent inactivation with a slight decrease of its amplitude; IC(50) = 38.2 +/- 3.5 microM, evaluated from changes of the time integral). The fast time constant of I (to) inactivation was significantly decreased in a concentration-dependent manner (IC(50) = 30.0 +/- 6.6 microM). Both blocks were use and frequency dependent at 3.3 Hz. We conclude that perphenazine causes concentration-, use-, and frequency-dependent block of I (Na) and I (to) . Computer simulations suggest that perphenazine interacts preferentially with I (Na) channels in inactivated states and with I (to) channels in both open and open-inactivated states.

• MeSH
• Antipsychotic Agents administration & dosage   toxicity   MeSH
• Potassium Channels drug effects   metabolism   MeSH
• Inhibitory Concentration 50 MeSH
• Myocytes, Cardiac drug effects   metabolism   MeSH
• Rats MeSH
• Patch-Clamp Techniques MeSH
• Perphenazine administration & dosage   toxicity   MeSH
• Computer Simulation MeSH
• Rats, Wistar MeSH
• Sodium Channels drug effects   metabolism   MeSH
• Heart Ventricles cytology   drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antipsychotic Agents MeSH
• Potassium Channels MeSH
• Perphenazine MeSH
• Sodium Channels MeSH