pharmacology

Efficient synthesis and first regioselective C-6 direct arylation of imidazo[2,1-c][1,2,4]triazine scaffold and their evaluation in H2O2-induced oxidative stress

Oxidative stress and apoptosis are both associated with various acute and chronic disorders. Thus, the aim of the present study is to synthesize imidazo[2,1-c][1,2,4]triazines derivatives and to evaluate their effects in H2O2-induced oxidative stress in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in stress and apoptosis-related proteins were investigated by PathScan® Stress and Apoptosis Signaling Antibody Array kit and Western Blot technique.

Impaired repair of DNA damage is associated with autistic-like traits in rats prenatally exposed to valproic acid

Prenatal exposure to the antiepileptic and mood stabilizer valproic acid (VPA) is an environmental risk factor for autism spectrum disorders (ASD), although recent epidemiological studies show that the public awareness of this association is still limited. Based on the clinical findings, prenatal VPA exposure in rodents is a widely used preclinical model of ASD. However, there is limited information about the precise biochemical mechanisms underlying the link between ASD and VPA.

In vitro and in vivo pharmacological activities of 14-o-phenylpropyloxymorphone, a potent mixed mu/delta/kappa-opioid receptor agonist with reduced constipation in mice

Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. However, opioid pain medications also cause detrimental side effects, thus highlighting the need of innovative and safer analgesics. Opioids mediate their actions via the activation of opioid receptors, with the mu-opioid receptor as the primary target for analgesia, but also for side effects.

Collaboration between a human group and artificial intelligence can improve prediction of multiple sclerosis course. A proof-of-principle study

Background: Multiple sclerosis has an extremely variable natural course. In most patients, disease starts with a relapsing-remitting (RR) phase, which proceeds to a secondary progressive (SP) form. The duration of the RR phase is hard to predict, and to date predictions on the rate of disease progression remain suboptimal. This limits the opportunity to tailor therapy on an individual patient's prognosis, in spite of the choice of several therapeutic options.

Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action

Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm.

Addiction research and theory: a commentary on the surgeon general's report on alcohol, drugs, and health

The Office of the Surgeon General recently produced its first Report on the consequences of alcohol and drug abuse on health, making several very laudable policy recommendations. The Report also emphasizes the importance of adequate funding for biomedical research, which is good news for both researchers and patients. However, the Report is marred by a biased viewpoint on the psychology and neurobiology of drug addiction.

Paradoxical sleep deprivation in rats causes a selective reduction in the expression of type-2 metabotropic glutamate receptors in the hippocampus

Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed
with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing
rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at
the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed
them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in

Sphingosine 1-phosphate receptors: do they have a therapeutic potential in cardiac fibrosis?

Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as
an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial

From pyrrolidinyl-benzodioxane to pyrrolidinyl-pyridodioxanes, or from unselective antagonism to selective partial agonism at ?4?2 nicotinic acetylcholine receptor

Each of the four aromatic eCH¼ of (S,R)-2-pyrrolidinyl-1,4-benzodioxane [(S,R)-6] and of its epimer at the dioxane stereocenter (S,S)-6, previously reported as a4b2 nAChR ligands, was replaced with nitrogen. The resulting four diastereoisomeric pairs of pyrrolidinyl-pyridodioxanes were studied for the nicotinic affinity and activity at a4b2, a3b4 and a7 nAChR subtypes and compared to their common carbaisostere.

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal.

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