PURPOSE: The locomotive activity changes after intravenous (i.v.) administration of @entity2727 ( @entity14501 ) in @entity35 were pharmacodynamically analyzed. METHODS: @entity14501 concentration in plasma, @entity14501 concentration and @entity935 (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of @entity14501 (2, 5 and 10 mg/kg doses) were used for the analysis. RESULTS: The transport of @entity14501 from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the @entity14501 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 @entity14501 . The inhibition constant (Ki) of @entity14501 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, @entity2915 and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of @entity14501 could be represented by this model. CONCLUSIONS: The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by @entity14501 , and may by useful for other DA reuptake inhibitors, such as @entity4944 and @entity888 .

Pharmacodynamic modeling for change of locomotor activity by @entity2727 in XXXX .

@entity888 :: ('MESH:D008694', 'Chemical') :: ['methamphetamine'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity14501 :: ('CHEBI:62995', 'Chemical') :: ['MPD'] @entity2915 :: ('MESH:D006948', 'Disease') :: ['hyperkinesia'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity4944 :: ('MESH:D000661', 'Chemical') :: ['amphetamine'] @entity2727 :: ('MESH:D008774', 'Chemical') :: ['methylphenidate']
@entity35 :: (10116,Species) :: ['rats']
