Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/pharmacokinetics , Central Nervous System Stimulants/therapeutic use , Child , Humans , Methylphenidate/administration & dosage , Methylphenidate/pharmacokinetics , Methylphenidate/therapeutic use , Pemoline/administration & dosage , Pemoline/pharmacokinetics , Pemoline/therapeutic useABSTRACT
Self-injurious behavior occurring in persons with severe mental retardation is a clinically significant and poorly understood problem. Multiple neurotransmitter systems have been implicated in the pathogenesis of this behavior, particularly dopaminergic, opioidergic, and serotonergic systems. Pemoline, a central stimulant, administered systemically at high doses reliably produces self-biting behavior in the rat. The systemic bolus of pemoline produces sustained neostriatal levels of pemoline for over 24 h in a continuous infusion paradigm. Studies of the effect of cortical lesions on pemoline-mediated behaviors reveal that cortical damage, as is common in profound mental retardation, lowers the threshold for pemoline-induced self-biting behavior. Data from the corticostriatal slice suggests that sustained exposure to pemoline produces a shift in N-methyl-D-aspartate receptor-mediated responses rendering them more susceptible to dopaminergic enhancement. Thus, dopaminergic and glutamatergic interactions appear to play an important role in the development and expression of self-biting in the pemoline model.
Subject(s)
Dopamine/physiology , Glutamic Acid/physiology , Self-Injurious Behavior/physiopathology , Animals , Central Nervous System Stimulants , Cerebral Cortex/pathology , Corpus Striatum/metabolism , Disease Models, Animal , Drug Interactions , Humans , Pemoline/pharmacokinetics , Pemoline/pharmacology , Self-Injurious Behavior/chemically induced , Self-Injurious Behavior/drug therapySubject(s)
Central Nervous System Stimulants/therapeutic use , Mental Disorders/drug therapy , Central Nervous System Stimulants/adverse effects , Central Nervous System Stimulants/pharmacokinetics , Depressive Disorder/blood , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Dextroamphetamine/adverse effects , Dextroamphetamine/pharmacokinetics , Dextroamphetamine/therapeutic use , Drug Interactions , Humans , Mental Disorders/blood , Mental Disorders/psychology , Methylphenidate/adverse effects , Methylphenidate/pharmacokinetics , Methylphenidate/therapeutic use , Pemoline/adverse effects , Pemoline/pharmacokinetics , Pemoline/therapeutic useABSTRACT
The onset, duration, and offset of pemoline action to improve cognitive performance is examined intensively in 25 prepubescent males suffering from attention-deficit disorder with hyperactivity (ADDH). The purpose was to characterize the pharmacodynamics of pemoline in ADDH patients through correlation of plasma pemoline concentration with psychometric measures of memory search efficiency and paired-associates learning, with the physiological effect of pemoline on dopaminergic transmission concurrently measured by analysis of plasma prolactin response. The effect of pemoline on neuroprocessing is apparent within the first 2 hours after administration with an inverse relationship between plasma pemoline and prolactin concentration present at hour one only (r = 0.84; p = 0.005). Pemoline therapy for 3 weeks does not significantly affect area under the curve for pemoline or prolactin nor did the effect on memory search efficiency decrease, suggesting no apparent tolerance.
Subject(s)
Attention Deficit Disorder with Hyperactivity/blood , Attention/drug effects , Motor Activity/drug effects , Pemoline/pharmacokinetics , Attention/physiology , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Child , Dose-Response Relationship, Drug , Humans , Male , Metabolic Clearance Rate , Methylphenidate/administration & dosage , Methylphenidate/pharmacokinetics , Motor Activity/physiology , Paired-Associate Learning/drug effects , Paired-Associate Learning/physiology , Pemoline/administration & dosageABSTRACT
Plasma pemoline levels were measured in 6- to 12-year-old, severely hyperactive males coincident with onset of abnormal involuntary movements. Acute exposure to pemoline (2 mg/kg orally) was associated with choreoathetoid movements of face, limbs, and trunk in five of 20 subjects in an acute study of pemoline pharmacokinetics. Also reported is a series of four chronically treated patients who developed choreiform movements and dyskinesias after variable periods of exposure from 3 weeks to 3 months with pemoline (1.5-2.0 mg/kg/day). Abnormal movements following acute or chronic exposure to pemoline cleared after pemoline discontinuation. Pemoline pharmacokinetics does not seem to be a primary determinant in the development of abnormal involuntary movements after chronic exposure. Total amount of pemoline absorbed may play a role in the development of choreoathetoid movements following acute exposure.
