No abstract

Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990-2012. Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described. Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

Mitochondria are membrane-enclosed organelle found in most eukaryotic cells, where they generate the majority of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. In addition, they are involved in a range of other processes, such as signalling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. Mitochondria have been implicated in several neuropsychiatric disorders, in particular, depression, anxiety, schizophrenia, autism, and Alzheimer's dementia. Furthermore, the presence of mutations at the level of mitochondrial or nuclear DNA (mtDNA and nDNA, respectively) has been linked to personality disorders, behavioral disturbances, thought alterations, impulsivity, learning impairment, cognitive failures until dementia. The aim of this paper is to review the literature on the relationship between psychiatric symptoms or syndromes and mtDNA mutations or mitochondrial alterations, while highlighting novel therapeutic targets for a broad range of disorders.

Background/Aims: The aim of this study was to investigate the serotonin transporter (SERT), by means of the ³H-paroxetine ([³H]-Par) binding to platelet membranes, in patients affected by pathological gambling (PG), as compared with a similar group of healthy control subjects. Methods: Seventeen PG patients were selected amongst those who were drug-free and at the first psychiatric interview in a Department of Addiction. The diagnosis was assessed according to DSM-IV criteria and PG severity was measured by means of the South Oaks Gambling Screen. The platelet [³H]-Par binding was carried out according to a standardized method. The binding parameters, the maximum binding capacity (B_max) and the dissociation constant (K_d), were obtained by means of the Scatchard analysis. Results: The B_max values of PG patients were significantly lower than that of healthy subjects, while the K_d values were not different in the two groups. No significant effect of age, sex or psychiatric comorbidity on B_max or K_d was observed; there were also no correlations between clinical and biological variables. Conclusions: PG patients showed a dysfunction at the level of the platelet SERT that would suggest the involvement of the 5-HT system in this condition.

The serotonin (5-HT) receptors of type 6 (5-HT6) are quite different from all other 5-HT receptors, as they include a short third cytoplasmatic loop and a long C-terminal tail, and one intron located in the middle of the third cytoplasmatic loop. A lot of controversies still exist regarding their binding affinity, effects of 5-HT6 ligands on brain catecholamines, behavioral syndromes regulated by them, and brain distribution. In spite of the lack of information on metabolic pattern of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic, antidepressant and anti-obese drugs. The present paper is a comprehensive review on the state of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.