Myo-inositol-1-phosphate (MIP) synthase inhibition: in-vivo study in rats.
Lithium and valproate are the prototypic mood stabilizers and have diverse structures and targets. Both drugs influence inositol metabolism. Lithium inhibits IMPase and valproate inhibits MIP synthase. This study shows that MIP synthase inhibition does not replicate or augment the effects of lithium in the inositol sensitive pilocarpine-induced seizures model. This lack of effects may stem from the low contribution of de-novo synthesis to cellular inositol supply or to the inhibition of the de-novo synthesis by lithium itself.
Einat
H
H
Department of Pharmacy Practice and Pharmaceutical Education, College of Pharmacy, University of Minnesota, Duluth, MN, USA. heinat@d.umn.edu
Tian
F
F
Belmaker
R H
RH
Frost
J W
JW
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D018692:Antimanic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D007296:Myo-Inositol-1-Phosphate Synthase / Q000187:drug effects* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy