Effect of Imipramine on the Membrane Anisotropy and on the Phospholipid Methylation in the Central Nervous System of the Rat

Abstract

An ex-vivo and in-vitro study of the effects of imipramine on the membrane anisotropy and phospholipid methylation in the rat cortical membranes was carried out. A comparative study of the membrane fluidity in various brain regions indicated different basal anisotropy of the areas and different reaction of these membranes to imipramine. It was found that imipramine when given to rats chronically (14 x 10 mg kg-1, i.p.) or added externally to the cortical membranes of naive rats or rats treated with a single dose of imipramine (10 mg kg-1, i.p.) decreased the anisotropy of cortical membranes. Chronic imipramine produced some changes of the membrane architecture in the cortex, whereas imipramine in different concentrations did not fluidize these membranes in-vitro. Imipramine in concentrations corresponding to its mean concentration in the rat brain after administration at a dose of 10 mg kg-1 i.p., potentiated phospholipid methylation in the cortical membranes of naive rats and rats receiving imipramine in a single dose of 10 mg kg-1 i.p. in an in-vitro study, whereas the prolonged administration of imipramine decreased the sensitivity of phospholipid methyltransferases to the stimulating effect of the drug in-vitro.

The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D2 dopamine receptors in the rat caudate putamen

“…The lack of significant alterations in the level of cyclic AMP in the slices of CP obtained from control animals induced by 10 μM GppNHp may result from mixed effect on different populations of G proteins. On the other hand, following administration of imipramine, such changes take place either in the fluidity of the cell membrane — as described previously by Melzacka and Nocon (1991) — or at the very level of G i proteins themselves, that inhibition of adenylate cyclase becomes apparent. Indeed, ex vivo (i.e.…”

Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor

“…Tricyclic antidepressants decreased the anisotropy values of HEK-5-HT 3A cells in the upper micromolar range, indicating an increase in membrane fluidity, as it has been observed in different membrane preparations from rat brains. 38,39 In addition, spin-label studies suggested an increase in membrane fluidity after a treatment with DMI and imipramine at low micromolar concentrations. 40 However, in rat synap- Values (mean7SEM; n=3-4) indicate percent of the control current; ND=not determined.…”