Chronic administration does not alter the accumulation of L-dopa into muscle

Authors

  • S. Rose,

    1. Parkinson's Disease Society Experimental Research Laboratories, Pharmacology Group, Biomedical Sciences Division, King's College, London, U.K.
    Search for more papers by this author
  • Dr. P. Jenner,

    Corresponding author
    1. Parkinson's Disease Society Experimental Research Laboratories, Pharmacology Group, Biomedical Sciences Division, King's College, London, U.K.
    • Pharmacology Group, Biomedical Sciences Division, King's College, Manresa Rd., London, SW3 6LX, U.K.
    Search for more papers by this author
  • C. D. Marsden

    1. Parkinson's Disease Society Experimental Research Laboratories, Pharmacology Group, Biomedical Sciences Division, King's College, London, U.K.
    Search for more papers by this author

Abstract

Rats were treated for 12 months with L-dopa (191.4–210.4 mg/kg/day) plus carbidopa (23.9–26.2 mg/kg/day), or carbidopa (24.4–26.3 mg/kg/day) alone. Four days after drug withdrawal, animals received an acute challenge with either L-dopa (50 mg/kg p.o.) alone or following acute carbidopa (25 mg/kg i.p.) pretreatment, and the uptake and metabolism of L-dopa in muscle was studied. Following the acute bolus challenge, plasma levels of L-dopa peaked between 0.5 and 3 h after L-dopa alone and between 1.5 and 2 h after L-dopa plus carbidopa. Peak levels in muscle were observed between 1.5 and 4 h after L-dopa administration, and this accumulation was enhanced by the acute pretreatment with carbidopa. Chronic administration of L-dopa plus carbidopa or carbidopa alone for 12 months had no effect on the accumulation of L-dopa into muscle following the acute challenge with L-dopa alone or after carbidopa pretreatment. 3-O-Methyldopa, dopamine, DOPAC, and HVA levels were elevated in both plasma and muscle following acute oral challenge with L-dopa or L-dopa plus carbidopa. Levels of these metabolites were unaffected by chronic administration of L-dopa plus carbidopa or carbidopa alone. In conclusion, chronic administration of L-dopa plus carbidopa did not alter the accumulation of L-dopa into muscle following an acute oral challenge with the drug, with or without carbidopa pretreament.

Ancillary