Pharmacokinetic profile of methyldopa in the brain of sinaortic-denervated rats.
Pharmacokinetics of methyldopa (MD) and the effect on the dopaminergic metabolism was studied in anesthetized sham-operated (SO) and sinoaortic-denervated (SAD) rats by using the microdialysis technique. A concentric microdialysis probe was placed in the striatum or in the posterior hypothalamus. Levels of MD, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC). Following the i.p. administration of MD (50 mg x kg(-1), i.p.), striatal dialysates showed that this drug rapidly reaches the brain. However, in SAD rats the MD levels of dialysates were lower and decreased more rapidly compared to SO rats. On the other hand, dialysates of posterior hypothalamus showed that in SAD animals the accumulation of MD was significantly greater than in SO rats.MD does not significantly reduce the striatal production of dopaminergic metabolite DOPAC in both groups of rats. The drug also induces a decrease of DOPAC levels in hypothalamic dialysates of SO and SAD animals. On the other hand, a no significative decay of HVA levels was seen in the striatal dialysate of both groups of experimental animals. In conclusion, this study by using a microdialysis technique shows that MD has different kinetic profiles in dialysates from posterior hypothalamus and striatum of SO and SAD rats at a dose that alters dopaminergic metabolism.
Opezzo
Javier A W
JA
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junĭn 956, 1113 Buenos Aires, Argentina. jopezzo@huemul.ffyb.uba.ar
Höcht
Christian
C
Taira
Carlos A
CA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism; D003714:Denervation / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008750:Methyldopa / Q000493:pharmacokinetics* / Q000494:pharmacology; D017551:Microdialysis; D011311:Pressoreceptors; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; D008750:Methyldopa; D004298:Dopamine; D006719:Homovanillic Acid