Effects of neuroleptics on blood glucose, free fatty acids and liver glycogen levels in the rat.
In fed rats the mechanisms of the action of spiroperidol (SPI), chlorpromazine (CPZ), fluphenazine (FLU) and thioridazine (TRZ) blood glucose, liver glycogen, serum free fatty acids (FFA) and K ion levels were investigated. Phenothiazines induced significant hyperglycemic responses with concomitant increase in liver glycogen, elevation of serum FFA and hypokalemia. CPZ and FLU were the most potent and TRZ was least potent in inducing above mentioned metabolic responses, which were most pronounced in 4--6 hr. SPI produced significant hyperglycemia for sorter period of time with a subsequent decrease of liver glycogen. An alpha-adrenergic antagonist, phentolamine prevented neuroleptic-induced hyperglycemia, impaired the increase of liver glycogen, partially diminished hyperlipemia and did not substantially change hypokalema occuring following neuroleptics. Antagonist of beta-adrenergic receptor, propranolol did not practically influence metabolic responses to neuroleptics. Adrenalectomy impaired substantially but did not abolish neuroleptic-induced hyperglycemia, indicating that also extraadrenal mechanisma, conceivable impairing glucose utilization and metabolism, are responsible for hyperglycemia induced by neuroleptics. This experiments suggest that phenothiazines may induce hyperglycemic response by activation of alpha-adrenergic receptors by contrast to alpha-adrenertic blocking action of these drugs in the central nervous system.
D000315:Adrenalectomy; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D013565:Sympatholytics / Q000494:pharmacology
D014150:Antipsychotic Agents; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D008112:Liver Glycogen; D013565:Sympatholytics; D011188:Potassium