New L-dopa codrugs as potential antiparkinson agents.
This paper reports the synthesis and preliminary evaluation of new L-dopa (LD) conjugates (1 and 2) obtained by joining LD with two different natural antioxidants, caffeic acid and carnosine, respectively. The antioxidant efficacy of compounds 1 and 2 was assessed by evaluating plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the rat. Rat striatal concentration of LD and dopamine (DA), and central nervous effects were evaluated after oral administration of the codrugs 1 and 2. The results suggest that, though our codrugs are devoid of significant antioxidant activity, they are able to induce sustained delivery of DA in rat striatum and can improve LD and DA release in the brain.
Sozio
Piera
P
Dipartimento di Scienze del Farmaco, Università G D'Annunzio, Chieti, Italy.
Iannitelli
Antonio
A
Cerasa
Laura Serafina
LS
Cacciatore
Ivana
I
Cornacchia
Catia
C
Giorgioni
Gianfabio
G
Ricciutelli
Massimo
M
Nasuti
Cinzia
C
Cantalamessa
Franco
F
Di Stefano
Antonio
A
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D002336:Carnosine / Q000737:chemistry / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007980:Levodopa / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D000978:Antiparkinson Agents; D002109:Caffeic Acids; D007980:Levodopa; D002336:Carnosine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C040048:caffeic acid; D004298:Dopamine