Major depressive disorder is often associated with deficits in social and cognitive functioning. Mice transgenic for acid sphingomyelinase (t-ASM) were previously shown to have a depressive-like phenotype, which could be normalized by antidepressant treatment. Here, we investigated whether t-ASM mice show deficits in social behavior and memory performance, and whether these possible deficits mi...

1. In isolated hearts of rabbits, perfusion with (-)-noradrenaline (0.0059 to 5.9 micronM) resulted in chronotropic and inotropic responses and a shortening of the interval between peak atrial and peak ventricular tensions (the A-V contraction interval). No dysrhythmias developed but at higher concentrations (590 micronM) 2 out of 7 hearts developed dysrhythmias (extrasystoles). 2. Perfusion wi...

The present study tested a hypothesis that excess accumulation of sphingolipid, ceramide and/or its metabolites contribute to the development of obesity and associated kidney damage. LC/MS spectroscopy analysis demonstrated that C57BL/6J mice on the high fat diet (HFD) had significantly increased plasma total ceramide levels compared to the low fat diet (LFD)-fed animals. Treatment of mice with...

BACKGROUND Tricyclic antidepressants (TCAs) are commonly used orally for treating chronic pain states, such as neuropathic pain. TCAs produce analgesia by various mechanisms, including sodium channels, N-methyl-d-aspartate receptors, biogenic amines, opioids, inflammatory mediators, and substance P. Studies have shown that intrathecal tricyclic administration effectively attenuates pain and the...

BACKGROUND Amitriptyline has been replaced in many countries by alternative and more expensive drugs based on claims of improved tolerability and toxicity and despite slightly reduced efficacy. Preliminary studies indicate that adverse effects could be linked to polymorphisms of drug-metabolizing enzymes, but information on their clinical impact remains scanty and includes mainly case reports. ...

The fluorescence polarization immunoassay (FPIA) developed by Abbott to diagnose intoxication with tricyclic antidepressants was adapted for therapeutic drug monitoring and validated with chromatograpic methods to investigate its potential for this use. We compared serum concentrations of tricyclic antidepressants in vivo and in vitro obtained by FPIA with those by gas chromatography and HPLC. ...

Central neuropathic pain in patients with multiple sclerosis (MS) is a common debilitating symptom, which is mostly treated with tricyclic antidepressants or antiepileptics. Unfortunately, the use of these drugs is often limited due to adverse events. We investigated the analgesic effect of topical amitriptyline 5% and 10% cream in a patient with central neuropathic pain due to MS. The analgesi...

The tricyclic antidepressant amitriptyline and the H1-receptor antagonist diphenhydramine are conjugated in human liver microsomes fortified with UDP-glucuronic acid at their tertiary amino groups with the formation of quaternary ammonium glucuronides. The kinetics of the reactions were found to be biphasic with apparent KM1 and KM2 values of 1.4 microM and 311 microM for amitriptyline and 2.6 ...

The aim of the present study was to assess the impact of combined therapy with rosuvastatin (10 mg/kg) and amitriptyline (10 mg/kg) on oxidation-reduction status in the blood of rats. After 2-week application of drugs alone or their combination, the activity of glutathione peroxidase (GPX), glutathione reductase (GR) and total antioxidant status (TAS) were determined. It was noticed that combin...

Because of less systemic side effects of topical medications in pain relief of the painful form of diabetic peripheral neuropathy, this study aimed to compare the effect of amitriptyline and capsaicin cream in relieving pain in this condition. In this randomized, double-blind and non -inferiority trial, 102 patients received amitriptyline 2% and capsaicin 0.75% creams 3 times a day for 12 weeks...