thiamylal and inositol-1-phosphate

Noradrenergic pathways in the brain have been thought to be related to the site of anesthetic action. Norepinephrine (NE) in the central nervous system stimulates phosphatidylinositol (PI) turnover through alpha 1-adrenergic receptors. The present study was designed to examine the effects of intravenous anesthetics on NE-induced PI turnover in rat cerebral cortical prisms. NE-induced inositol monophosphate (IP1) formation was inhibited by droperidol (dose for 50% inhibition [ID50], 0.0258 +/- 0.00023 microM [mean +/- SE]), fentanyl (2.36 +/- 0.0017), diazepam (201 +/- 2.12), and thiamylal (231 +/- 1.94) in a dose-dependent manner, but was not affected by ketamine. Naloxone or flumazenil did not attenuate the inhibitory effect of fentanyl or diazepam on NE-induced IP1 formation. The results suggest that these effects on the PI turnover in the cortex may be related to their pharmacologic properties including the anesthetic action.

Topics: Anesthetics, Intravenous; Animals; Cerebral Cortex; Diazepam; Dose-Response Relationship, Drug; Droperidol; Fentanyl; Flumazenil; Inositol Phosphates; Ketamine; Male; Naloxone; Norepinephrine; Phosphatidylinositols; Prazosin; Rats; Rats, Wistar; Thiamylal

Combined effects of adrenergic and intravenous anesthetic agents on phosphatidylinositol (PI) turnover were studied using rat liver prisms incubated with [3H]myo-inositol. Rat liver prisms responded to epinephrine, norepinephrine and phenylephrine dose-dependently with an increase in inositol monophosphate (IP1) formation but they did not respond to ephedrine. Dopamine-induced effects were seen only at concentrations as high as 10(-4) mol.l-1. The enhancement of IP1 formation induced by epinephrine was potentiated by thiamylal at concentrations of 10(-5) mol.l-1 and 10(-4) mol.l-1, remained unaffected by ketamine, fentanyl or midazolam, but was dose-dependently inhibited by droperidol. The present results from in vitro studies of liver cell metabolism suggest that alpha-adrenergic agents in combination with barbiturates may potentiate liver cell damage by activation of PI turnover and interrelated intracellular Ca++ accumulation.

Topics: Anesthesia, Intravenous; Anesthetics; Animals; Dose-Response Relationship, Drug; Droperidol; Drug Interactions; Ephedrine; Epinephrine; Fentanyl; Inositol Phosphates; Ketamine; Liver; Male; Midazolam; Norepinephrine; Phenylephrine; Phosphatidylinositols; Rats; Rats, Sprague-Dawley; Sympathomimetics; Thiamylal