Direct Effects of Diphenylhydantoin (Phenytoin) on the Ion‐Transporting ATPases of Cultured Osteoblast‐like Cells

Abstract

Diphenylhydantoin (phenytoin) added to cultures of osteoblast-like cells at a concentration of 10 microM, at the high end of the therapeutic range in plasma of unbound phenytoin (4-8 microM), caused reductions in Na+, K+-ATPase and alkaline phosphatase activities and increases in Ca2+-ATPase and HCO3--ATPase activities in homogenates of whole cells and in subcellular fractions of cultured osteoblast-like cells. These data suggest that, if these changes occur in vivo, the osteomalacia associated with treatment with diphenylhydantoin may be mediated in part by direct effects on the ability of bone cells to transport ions.

Effect of Prolonged Anticonvulsant Medication in Epileptic Patients: Serum Lipids, Vitamins B6, B12, and Folic Acid, Proteins, and Fine Structure of Liver

“…(1973) also reported similar changes on phenytoin therapy. In vitro studies on cultured osteoblastlike cells suggest that such PHT-related osteomalacia may be mediated partly by direct depression of the bone cells to transport ions (Anderson and Woodbury, 1984).…”

Update on the mechanisms of action of antiepileptic drugs

“…Lamotrigine (LTG) exerts its antiepileptic effects by voltage-and frequency-dependent blockade of neuronal sodium channels, inhibiting sustained repetitive neuronal firing without influencing the amplitude or duration of single action potentials [57][58][59][60]. The broad cIinicaf spectrum of LTG suggests that its interaction with the sodium channel may differ from that of PHT and CBZ.…”