Pharmacodynamics of the hypotensive effect of levodopa in parkinsonian patients.
Blood pressure effects of i.v. levodopa were examined in parkinsonian patients with stable and fluctuating responses to levodopa. The magnitude of the hypotensive effect of levodopa was concentration dependent and was fit to an Emax model in fluctuating responders. Stable responders demonstrated a small hypotensive response. Baseline blood pressures were higher in fluctuating patients; a higher baseline blood pressure correlated with greater hypotensive effects. Antiparkinsonian effects of levodopa temporally correlated with blood pressure changes. Phenylalanine, a large neutral amino acid (LNAA) competing with levodopa for transport across the blood-brain barrier, reduced the hypotensive and antiparkinsonian effects of levodopa. We conclude that levodopa has a central hypotensive action that parallels the motor effects in fluctuating patients. The hypotensive effect appears to be related to the higher baseline blood pressure we observed in fluctuating patients relative to stable patients.
Irwin
R P
RP
Department of Neurology, Oregon Health Sciences University, Portland.
Nutt
J G
JG
Woodward
W R
WR
Gancher
S T
ST
D000596:Amino Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D007262:Infusions, Intravenous; D007980:Levodopa / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010649:Phenylalanine / Q000494:pharmacology
D000596:Amino Acids; D007980:Levodopa; D010649:Phenylalanine