The α6 GABAA Receptor Positive Allosteric Modulator DK-I-56-1 Reduces Tic-Related Behaviors in Mouse Models of Tourette Syndrome

Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric modulators (PAMs) of GABAA receptors containing α6 subunits (α6 GABAARs) oppose the behavioral effects of dopamine. Building on this evidence, in the present study, we tested the efficacy of DK-I-56-1, a highly selective PAM for α6 GABAARs, in mouse models of TS exhibiting tic-related responses. DK-I-56-1 significantly reduced tic-like jerks and prepulse inhibition (PPI) deficits in D1CT-7 transgenic mice, a well-documented mouse model of TS. DK-I-56-1 also prevented the exacerbation of spontaneous eyeblink reflex induced by the potent dopamine D1 receptor agonist SKF 82958, a proxy for tic-like responses. We also showed that both systemic and prefrontal cortical administration of DK-I-56-1 countered the PPI disruption caused by SKF 82958. Although the effects of DK-I-56-1 were akin to those elicited by dopaminergic antagonists, this drug did not elicit extrapyramidal effects, as measured by catalepsy. These results point to α6 GABAAR PAMs as promising TS therapies with a better safety profile than dopaminergic antagonists.

Vitex agnus castus and Some Female Disorders: A Review

Vitex agnus castus L., is a deciduous tree which has been utilized in ancient Greece, Iran, Egypt and Rome for over 2500 years for a large variety of female reproductive system health difficulties. In Saudi Arabia, many women have menstrual cycle disturbances and menopausal dysfunction and many have polycystic ovary syndrome at young age. Using Vitex is not in Saudi tradition like other Arab countries. Recently, just few people used this herb for treating some infertility problems. A variety of beneficial effects of this curative herb have been reported in clinical studies, including antioxidant, anti-inflammatory, hypolipidemic, anti-diabetic, hormonal modulatory, anti-nociceptive and opioidergic activities, preventing oxidative stress and nonalcoholic fat liver disease. Adverse effects of the plant are mild and reversible. The advantages of this herb as natural medicine attract the people and make it one of best choose and utilize widely in women disorders specially that related with menopauses. Its constituents could interact with dopaminergic antagonists and exhibited progesteronic and estrogenic activities. This brief review introduces this plant to Saudi society and others to expand it usage and discusses the potential effect of the plant to cure some of the women disorders displaying its main ingredients and the side effects.

Asenapine modulates nitric oxide release and calcium movements in cardyomyoblasts

ObjectiveTo examine the effects of asenapine on NO release and Ca2+ transients in H9C2, which were either subjected to peroxidation or not.Materials and methodsH9C2 were treated with asenapine alone or in presence of intracellular kinases blockers, serotoninergic and dopaminergic antagonists, and voltage Ca2+ channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca2+ were measured through specific probes.ResultsIn H9C2, asenapine differently modulated NO release and Ca2+ movements depending on the peroxidative condition. The Ca2+ pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors and voltage Ca2+ channels blockers.ConclusionsOn the basis of our findings we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca2+ homeostasis in H9C2; this would be of particular clinical relevance, when considering their role in cardiac function modulation.Disclosure of interestThe authors have not supplied their declaration of competing interest.