We studied the effects of experimental diabetes on the pharmacokinetics of biperiden (BP) and scopolamine (SP) and brain muscarinic receptor alterations in rats after the injection of streptozotocin (STZ) (60mg kg−1 i.v.). The serum levels of BP and SP differed significantly between the rats 14 weeks after the STZ treatment and age‐matched control rats. The values of total body clearance (CLtot) of BP and SP were significantly increased by STZ treatment. The values of volume of distribution (Vdss) of SP were slightly increased in the STZ‐treated rats, although Vdss of BP was decreased. Because of the high lipophilicity of BP, Vdss of BP may be decreased due to the reduced fat tissue volume caused by STZ treatment. The density of the muscarinic receptors in whole brain was measured by a radioligand receptor binding assay using [3H]‐quinuclidinyl‐benzylate ([3H]‐QNB). The density in the diabetic rats two weeks after the STZ treatment was significantly decreased compared to age‐matched control rats. However in the diabetic rats 14 weeks after the STZ treatment, there was no difference in the density of muscarinic receptors. The IC50 of muscarinic antagonist for the binding of [3H]‐QNB to the receptor did not change on STZ treatment. Modulation of the receptor following repeated anticholinergic drug exposure was studied. In control rats, the number of muscarinic receptors in the brain increased by 6.9% on chronic treatment with BP for two weeks. When diabetic rats were treated with BP and SP, the number of muscarinic receptors in the brain increased by 9.6% and 33.8%, respectively.
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