Codrugs linking L-dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson's disease.
A series of multifunctional codrugs (1-6) were synthesized to overcome the pro-oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an antioxidant effect superior to that of N-acetylcysteine (NAC). After intracerebroventricular injection of codrug 4, the levels of DA in the striatum were higher than those in LD-treated groups, indicating that this compound has a longer half-life in brain than LD.
Pinnen
Francesco
F
Dipartimento di Scienze del Farmaco, Universita G. D'Annunzio, Via dei Vestini 31, 66100 Chieti, Italy.
Cacciatore
Ivana
I
Cornacchia
Catia
C
Sozio
Piera
P
Cerasa
Laura Serafina
LS
Iannitelli
Antonio
A
Nasuti
Cinzia
C
Cantalamessa
Franco
F
Sekar
Durairaj
D
Gabbianelli
Rosita
R
Falcioni
Maria Letizia
ML
Di Stefano
Antonio
A
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007276:Injections, Intraventricular; D007980:Levodopa / Q000032:analysis*; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013455:Sulfur / Q000032:analysis*
D000975:Antioxidants; D000978:Antiparkinson Agents; D007980:Levodopa; D013455:Sulfur