PMID: 9434281Jan 22, 1998Paper

Pharmacodynamic modeling for change of locomotor activity by methylphenidate in rats

Pharmaceutical Research
T AoyamaT Iga

Abstract

The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (Ki) of MPD for DA reuptake was estimated to be 41.3 +/- 73.8 nM (mean +/- SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dos...Continue Reading

Citations

Feb 10, 2000·Journal of Psychopharmacology·N D VolkowG J Wang
Jan 25, 2019·The Journal of Pharmacology and Experimental Therapeutics·Ryosuke ShimizuShuichi Ohnishi

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