7 ng/mL at 25 mg, and 50.5 ng/mL at 75 mg. Estimated ED50 was 76.8 mg of administration dose and 59.8 ng/mL of plasma concentration.
NET occupancy by nortriptyline corresponding to the administration dose of 10-75 mg or plasma concentration was observed from 16% to 41%.”
“H-1 NMR spectroscopy was applied to investigate the changes of cerebral metabolites in brain hippocampus, nucleus accumbens (NAC) and prefrontal cortex (PFC) of the rats subjected to subcutaneous YH25448 in vitro twice-daily injections of 2.5 mg/kg methamphetamine (MAP) for 7 days. The results indicated that MAP exposure induced significant behavioral sensitization and altered cerebral metabolites in rats. The neurotransmitters glutamate,
glutamine and GABA significantly TEW-7197 ic50 decreased in hippocampus, NAC and PFC. Specifically, increased succinic acid semialdehyde, a metabolism
product of GABA, was observed in hippocampus. Additionally, decreased serotonin was observed in both NAC and PFC, whereas decreased dopamine was only observed in NAC after repeated MAP treatment. Glutathione obviously decreased in above brain regions, whereas acetylcysteine declined in hippocampus and NAC, and taurine declined in NAC and PFC. Homocysteic acid was elevated in hippocampus and NAC by repeated MAP administration. Membrane ingredients like phosphocholine elevated in response to MAP administration in NAC and PFC. N-Acetyl-aspartate, a marker of neuronal viability, decreased in the three regions; however, myo-inositol, a glial cell marker, increased
in hippocampus and PFC. Tricarboxylic acid cycle intermediate products, such as alpha-ketoglutarate, succinate, citrate and the methionine significantly decreased in above three brain regions after MAP administration; however, ADP Megestrol Acetate decreased in hippocampus. These results indicate that repeated MAP treatment causes neurotransmitters disturbance, imbalance between oxidative stress and antioxidants, and gliosis in hippocampus, NAC and PFC. Profound metabolic changes detected across brain regions provide the first evidence of metabonomic changes in MAP-induced sensitized rats. (c) 2013 Elsevier Inc. All rights reserved.”
“Modafinil (ProvigilA (R)) is a wake-promoting drug characterized by cognitive enhancing abilities. Recent clinical data have supported the use of modafinil for treatment of chronic psychostimulant addiction and relapse prevention.
We used an intravenous methamphetamine (meth) self-administration procedure to assess the dose-dependent effects of modafinil on reinstatement following abstinence and after extinction on conditioned-cue and meth-primed reinstatement of meth seeking.
Modafinil attenuated active lever responding in multiple reinstatement conditions-context-induced, conditioned cue, and meth prime. The most pronounced and consistent effect was on meth-primed reinstatement, and modafinil did not reinstate meth seeking when tested alone.