These results provide first insights into the mechanism of BTX-A’s central antinociceptive activity. (C) 2013 Elsevier Ltd. All rights reserved.”
“The ameliorating effect of phosphatidylserine (PS) isolated from krill (KR-PS) on the learning and memory deficits associated with normal aging in rats was investigated, as compared with soybean PS (SOY-PS). Rats were orally administered with KR-PS (20, 50 mg kg(-1)) and SOY-PS (50 mg kg(-1)) daily, for 7 days, 30 min before behavioral assessment using the Morris water maze (MWM). Changes
in the cholinergic system were examined by measuring choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunoreactivity in the hippocampus. The daily administration of KR-PS produced a significant improvement in the escape latency for finding SRT1720 the platform in the MWM, as compared with SOY-PS. Consistent with the behavioral results, KR-PS treatments significantly alleviated age-associated losses of cholinergic immunoreactivity, and muscarinic Veliparib acetylcholine receptor type 1 (mAChR-M1) and choline transporter (CHT) mRNA expression in the hippocampus. These findings demonstrate that KR-PS showed significant neuroprotective
activity against the neuronal and cognitive impairments that occur with normal aging in rats; comparable results were obtained with SOY-PS. These data indicate that oral administration of PS derived from marine life could substitute for bovine cerebral cortex PS (BC-PS) as therapy for the improvement of diminished memory function in elderly people. (C) 2010 Elsevier Inc. All rights reserved.”
“Levomilnacipran (LVM; F2695) is the more active enantiomer of the serotonin/norepinephrine (5-HT/NE) reuptake inhibitor (SNRI) milnacipran and is currently under development for the treatment of major depressive disorder. LVM was benchmarked against two other SNRIs, duloxetine and venlafaxine, in selleck kinase inhibitor biochemical, neurochemical and pharmacological assays. LVM exhibited high affinity for human NE
(K-i = 92.2 nM) and 5-HT (11.2 nM) transporters, and potently inhibited NE (IC50 = 10.5 nM) and 5-HT (19.0 nM) reuptake (human transporter) in vitro. LVM had 2-fold greater potency for norepinephrine relative to serotonin reuptake inhibition (i.e. NE/5-HT potency ratio: 0.6) and 17 and 27 times higher selectivity for NE reuptake inhibition compared with venlafaxine and duloxetine, respectively. LVM did not exhibit affinity for 23 off-target receptors. LVM (i.p.) increased cortical extracellular levels of 5-HT, and NE (minimal effective doses: MEDs = 20 and 10 mg/kg, respectively). In anti-depressive/anti-stress models, i.p. LVM diminished immobility time in the mouse forced swim (MED = 20 mg/kg) and tail suspension (MED = 2.5 mg/kg) tests, and reduced shock-induced ultrasonic vocalizations in rats (MED = 5 mg/kg). Duloxetine and venlafaxine were less potent (MEDs >= 10 mg/kg). At doses active in these three therapeutically-relevant models, LVM (i.p.