1,888 research outputs found
Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy
No full textGender-related differences in the pharmacological effects of drug are an emerging topic. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of methadone, a long-acting opioid agonist that is prescribed as a treatment for opioid dependence and the management of chronic pain.Method: We performed a search in the Medline database from 1990 to 2014 in order to find published literature related to gender differences in pharmacokinetics and pharmacodynamics of methadone. Results: None of the studies were carried out with the primary or secondary aim to identify any gender differences in the pharmacokinetic profile of methadone. Importantly; high inter-subjects variability in PK parameters was found also intra female population. The reported differences in volume of distribution could be ascribed to the physiological differences between men and women in body weight and composition, taking into account that the dose of methadone was established irrespective of body weight of patients (Peles & Adelson, 2006). On the other hand, the few studies present in literature found no gender difference in some direct pharmacodynamic parameters. Some reports have suggested that female gender is associated with an increased risk for long-QT (LQT)-related cardiac arrhythmias in methadone maintenance subjects.Conclusion: Even though it may be too simplistic to expect variability only in one parameter to explain inter-individual variation in methadone response, we believe that a better knowledge of gender-related differences might have significant implications for better outcomes in opioid dependence substitution therapy in women
Unlocking the secrets of dopamine in Alzheimer's Disease
No full textDopamine (DA) is a neurotransmitter belonging to the catecholamine family that plays essential functions in the central nervous system. The main source of DA in the brain derives from dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) that project to different brain regions and exert distinct functions. The VTA targets the hippocampus, nucleus accumbens and cerebral cortex and mediates the control of motivation and reward. In contrast, the SNpc projects mainly to the caudate and putamen nuclei of the striatum and is involved primarily in the control of voluntary movement
SUMO: A (Oxidative) Stressed Protein
No full textRedox species are produced during the physiological cellular metabolism of a normal tissue. In turn, their presence is also attributed to pathological conditions including neurodegenerative diseases. Many are the molecular changes that occur during the unbalance of the redox homeostasis. Interestingly, posttranslational protein modifications (PTMs) play a remarkable role. In fact, several target proteins are modified in their activation, localization, aggregation, and expression after the cellular stress. Among PTMs, protein SUMOylation represents a very important molecular modification pathway during "oxidative stress". It has been reported that this ubiquitin-like modification is a fine sensor for redox species. Indeed, SUMOylation pathway efficiency is affected by the exposure to oxidative species in a different manner depending on the concentration and time of application. Thus, we here report updated evidence that states the role of SUMOylation in several pathological conditions, and we also outline the key involvement of c-Jun N-terminal kinase and small ubiquitin modifier pathway cross talk
Ginkgolic Acid Protects against Aβ-Induced Synaptic Dysfunction in the Hippocampus
No full textGinkgo leaf is the most used form of supplement for cognitive ailments. The standardized extract formulation EGb 761 is a dietary supplement with proven benefit in several neurological and psychiatric conditions including memory decline in Alzheimer's disease, schizophrenia and dementia. Ginkgolic acid (GA) is a component of this extract which shows pleiotropic effects including antitumoral and anti-HIV action; however, its effect on memory is still unknown. Here, we carried out an electrophysiological analysis to investigate the effects of GA on long term potentiation and synaptic transmission at CA1 hippocampal synapses. We also evaluated the potential rescuing effect of GA on the synaptic dysfunction following in vitro application of Aβ. Data obtained indicate that GA exerts neuroprotective effects against Aβ-induced impairment of neurotransmitter release and synaptic plasticity
Therapeutic potential of targeting hydrogen peroxide metabolism in the treatment of brain ischaemia
No full textFor many years after its discovery, hydrogen peroxide (H₂O₂) was viewed as a toxic molecule to human tissues; however, in light of recent findings, it is being recognized as an ubiquitous endogenous molecule of life as its biological role has been better elucidated. Indeed, increasing evidence suggests that H₂O₂ may act as a second messenger with a pro-survival role in several physiological processes. In addition, our group has recently demonstrated neuroprotective effects of H₂O₂ on in vitro and in vivo ischaemic models through a catalase (CAT) enzyme-mediated mechanism. Therefore, the present review summarizes experimental data supporting a neuroprotective potential of H₂O₂ in ischaemic stroke that has been principally achieved by means of pharmacological and genetic strategies that modify either the activity or the expression of the superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT enzymes, which are key regulators of H₂O₂ metabolism. It also critically discusses a translational impact concerning the role played by H₂O₂ in ischaemic stroke. Based on these data, we hope that further research will be done in order to better understand the mechanisms underlying H₂O₂ functions and to promote successful H₂O₂ signalling based therapy in ischaemic stroke
Gender difference in prescription opioid abuse: A focus on oxycodone and hydrocodone
No full textSeveral data gathered in the last decade indicate an increase of abuse of prescription opioid drugs oxycodone (OXY) and hydrocodone (HYDRO) in women. However, to date there are no conclusive evidences investigating the gender-dependent abuse liability of prescription opioids. This study aims to supply a specific focus on women's data through a selective summary of the literature analyzing gender differences in the pharmacokinetic and pharmacodynamic dimension of OXY and HYDRO. Findings from this study suggest that the majority of OXY and HYDRO pharmacokinetic and pharmacodynamic effects do not differ according to gender, though confirming a significant difference in the incidence of adverse effects as demonstrated by the increased gastrointestinal adverse reactions in female subjects. Although the majority of recent clinical studies include an equal number of female and male subjects, the main outcome parameters do not relate specifically to gender differences. Due to the gender influence in activity of CYP3A4 and its crucial role in metabolism of both OXY than HYDRO, we suggest that assessing pharmacokinetic and pharmacodynamic interactions in clinical studies may be useful to clarify the effect of the higher CYP3A4 activity in female in relation to CYP2D6 genotype. Overall, considering the paucity of data regarding gender differences in European Union, this work highlights that impact of new abuse deterrent formulations should be assessed with a special focus on data concerning female subjects
Editorial: targeting synaptic dysfunction and neural connectivity in neurological and psychiatric disorders
No full text[No abstract available
Genders and the concurrent use of cocaine and alcohol: Pharmacological aspects
No full textGender-related differences in the pharmacological effects of addictive drug are an emerging issue. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of alcohol and cocaine intake since they cause complex pharmacological interactions, not least the formation of the active metabolite cocaethylene
The Blockade of K+-ATP channels has neuroprotective effects in an in vitro model of brain ischemia
No full textThere is a common belief that the opening of K(+)-ATP channels during an ischemic episode has protective effects on neuronal functions by inducing a reduction in energy consumption. However, recent studies have also proposed that activation of these channels might have deleterious effects on cell's survival possibly after a stroke or during long-lasting neurodegenerative processes. Considering these contrasting results, we have used a hippocampal in vitro slice preparation in order to investigate the possible effects of K(+)-ATP channel blockers on the electrophysiological and morphological changes induced by a transient episode of ischemia (oxygen and glucose deprivation) on CA1 pyramidal neurons. Therefore, we found that tolbutamide and glibenclamide, both nonselective K(+)-ATP channel blockers, produce neuroprotective effects against in vitro ischemia. Interestingly, the mitochondrial K(+)-ATP channel blocker 5-hydroxydecanoate and various K(+) channel blockers did not exert neuroprotection. Our results are consistent with the concept that a decreased activity of the plasmalemmal K(+)-ATP conductances may have a protective effect during episodes of transient cerebral ischemia
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