RESUMO
Suppression of growth without significant alterations in hormonal patterns has been demonstrated for the neurostimulant drug pemoline. Comparison of the in vitro effect of pemoline, methylphenidate, and methamphetamine on somatomedin-stimulated sulfate uptake by cartilage showed all three drugs to be inhibitory. Sulfate uptake by cartilage can be directly related to growth and glycosaminoglycan biosynthesis. Assay of two of the enzymes involved in the glycosaminoglycan biosynthetic pathway showed that methamphetamine and methylphenidate caused a marked depression of xylosyl- and galactosyltransferase enzyme activity. These data suggest an interference with cartilage metabolism as one possible mechanism for the growth retardation observed in children on neurostimulant drug therapy.
Assuntos
Cartilagem/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Animais , Embrião de Galinha , Depressão Química , Relação Dose-Resposta a Droga , Galactosiltransferases/metabolismo , Glicosaminoglicanos/biossíntese , Metanfetamina/farmacologia , Metilfenidato/farmacologia , Pemolina/farmacologia , Pentosiltransferases/metabolismo , Somatomedinas/farmacologia , Sulfatos/metabolismo , Uridina Difosfato XiloseRESUMO
Decreased longitudinal growth was observed in 24 hyperkinetic children receiving pemoline therapy. Mean height velocity was 3.67 +/- 0.25 cm/year during therapy but 5.35 +/- 0.42 cm/year after treatment had been discontinued (P less than 0.01). There appeared to be an inverse relationship between growth velocity and drug dosage. All patients receiving less than the median dose of 3.72 mg/kg grew 4 cm/year or more, while seven of 12 patients receiving more than this dose grew at a slower rate. Body weight, basal and stimulated growth hormone values, and plasma somatomedin concentrations were not significantly altered by pemoline treatment, suggesting that this drug may have a direct effect on cartilage metabolism.