Effects of valproate derivatives on human brain myo-inositol-1-phosphate (MIP) synthase activity and amphetamine-induced rearing.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 4
Abstract
We have recently shown that valproate (VPA) decreases intracellular concentrations of inositol, like lithium but via a different mechanism, namely by inhibiting myo-inositol-1-phosphate (MIP) synthase. Valnoctamide (VCD) and valrocemide (VGD) are VPA derivatives which are anticonvulsants and have been shown in animal models to be significantly less teratogenic than VPA. We now show that 1 mM of either VCD or VGD drastically inhibits human brain crude homogenate MIP synthase activity. We studied the mechanism of the effect of VCD and found that it reduced the enzyme activity by an apparent competitive mode of inhibition at concentrations within the therapeutic range of VPA(K(i) = 0.18 mM). We studied the behavioral effect of VGD and found that both lithium and VGD attenuated amphetamine-induced increase in rearing. These data support clinical study of these VPA-derivatives in bipolar disorder.
Authors and Affiliations
Shaltiel Galit, Mark Shirley, Kofman Ora, Robert Belmaker, Agam Galila
Keywords
Related Articles
- EP ID EP96649
- DOI -
- Views 104
- Downloads 0
Anti-nephrolithic potential of resveratrol via inhibition of ROS, MCP-1, hyaluronan and osteopontin in vitro and in vivo.
Though resveratrol is known to have anti-cancer, anti-diabetic, anti-oxidant and anti-inflammatory activities, the inhibitory mechanism of resveratrol in kidney stone formation has not been elucidated so far.
Frequency-dependent inhibition of antidromic hippocampal compound action potentials by anti-convulsants.
Using rat hippocampal slices, extracellularly recorded antidromic compound action potentials (cAP) were produced in CA1 pyramidal cell populations by electrical stimulation of the alveus at 0.5 Hz. These responses were a...
Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice.
Orphenadrine is an anticholinergic drug used in the treatment of Parkinson's disease, and is also known to exert nonspecific antagonistic activity at the phencyclidine binding site of the N-methyl-D-aspartate (NMDA) rece...
Gestational manganese intoxication and anxiolytic-like effects of diazepam and the 5-HT1A receptor agonist 8-OH-DPAT in male Wistar rats.
In the present study, the effects of prenatal manganese (Mn) intoxication on the anxiolytic-like effects of diazepam and the 5-HT(1A) receptor agonist R-(+)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) were examined.Wista...
Dual effects of heparin on BMP-2-induced osteogenic activity in MC3T3-E1 cells.
Heparin displays several types of biological activities by binding to various extracellular molecules, including pivotal roles in bone metabolism. We have previously reported that heparin competitively inhibits the bindi...