Isomeric specificity of diphenylmethylpiperidine in the production of rat pancreatic islet cell toxicity.
The relationship between chemical structure and the pancreotoxic potential of positional isomers of diphenylmethylpiperidine was investigated in rats. The chemical synthesis of these compounds and their N-methylated analogs is reported. Oral administration of 4-diphenylmethylpiperidine and its N-methylated derivative (130 and 260 micronmoles/kg) to rats for 14 days resulted in hyperglycemia, reduced pancreatic insulin content and the formation of large vacuoles in the cytoplasm of pancreatic islet cells. No effect on beta cell morphology or insulin content was observed after administration of 2- and 3-diphenylmethylpiperidine and their N-methylated analogs.
D000818:Animals; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D007536:Isomerism; D008297:Male; D010880:Piperidines / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship; D014617:Vacuoles
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D007328:Insulin; D010880:Piperidines