Esters of L-dopa: structure-hydrolysis relationships and ability to induce circling behaviour in an experimental model of hemiparkinsonism.
A number of carboxylate esters of L-dopa, some of which are novel, were examined for their physicochemical and biological properties. A few esters of tyrosine and phenylalanine were included for comparison. The compounds displayed great differences in their lipophilicity and stability towards chemical and enzymatic (human plasma) hydrolysis. Within subseries, relationships exist between structural properties and rate constants of chemical or enzymatic hydrolysis. In an experimental model of hemiparkinsonism (circling behaviour in rats), some of the L-dopa esters (the isopropyl, sec-butyl and 2-(tetrahydropyranyl)methyl esters) showed an activity distinctly greater than that of L-dopa, although the difference was not statistically significant.
Brunner-Guenat
M
M
Institut de Chimie Thérapeutique, Section de Pharmacie, Université de Lausanne, Switzerland.
Carrupt
P A
PA
Lisa
G
G
Testa
B
B
Rose
S
S
Thomas
K
K
Jenner
P
P
Ventura
P
P
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004195:Disease Models, Animal; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007980:Levodopa / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000503:physiopathology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013329:Structure-Activity Relationship
D004952:Esters; D011355:Prodrugs; D007980:Levodopa