Alterations in cartilage metabolism by neurostimulant drugs.
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.
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002642:Chick Embryo; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005700:Galactosyltransferases / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D008694:Methamphetamine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D010389:Pemoline / Q000494:pharmacology; D010430:Pentosyltransferases / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D014540:Uridine Diphosphate Xylose
D000697:Central Nervous System Stimulants; D006025:Glycosaminoglycans; D013002:Somatomedins; D013431:Sulfates; D008774:Methylphenidate; D014540:Uridine Diphosphate Xylose; D008694:Methamphetamine; D010389:Pemoline; D005700:Galactosyltransferases; D010430:Pentosyltransferases