title: Effects of antidepressant drugs on inositol phospholipid hydrolysis in rat cerebral cortical slices.
abstract: The effects of several different types of antidepressant drugs on phosphoinositide hydrolysis by slices of rat cerebral cortex was investigated by prelabeling inositol phospholipids with [3H]inositol and then measuring the formation of [3H]inositol phosphates (a total fraction consisting of the mono- and poly-phosphates was collected) in the presence of 10 mM LiCl. All of the drugs tested (amitriptyline, trimipramine, mianserin, desipramine, tranylcypromine, and citalopram) inhibited NE-stimulated [3H]inositol phosphate formation. This inhibition appeared to be due to antagonism of alpha 1-receptors. In addition to inhibiting the effects of NE, the tricyclic antidepressants themselves were able to stimulate [3H]inositol phosphate formation. This stimulation occurred at drug concentrations higher than that needed to inhibit stimulation by NE. Stimulatory effects of the antidepressants themselves were not blocked by the alpha 1-antagonist, prazosin. An examination of the types of inositol phosphates formed revealed that formation of inositol monophosphate was stimulated, but that inositol biphosphate production was decreased by tricyclic antidepressants compared to control.
authors.affiliation: Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
authors.forename: L E
authors.initials: LE
authors.lastname: Dyck
authors.forename: A A
authors.initials: AA
authors.lastname: Boulton
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014299:Trimipramine / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D003984:Dibenzazepines; D007295:Inositol Phosphates; D010743:Phospholipids; D015283:Citalopram; D014299:Trimipramine