Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion.
The spatial distributions of 3 model drugs, [14C]dopamine hydrochloride (DA), [3H]sodium methotrexate (MTX) and [14C]antipyrine (AP), were determined after 6 days continuous microperfusion of the diencephalon of rabbits. The basic pattern of distribution was the same for each drug: the tissue concentration, expressed as a function of the perfusate concentration, was maximal at the cannula tip, and declined sharply with radial distance from the tip. However, at any given distance, concentrations of radioisotopes derived from DA and MTX, both ionized, lipid-insoluble drugs, were one to two orders of magnitude higher than those derived from AP, a lipid-soluble drug. Although concentrations of isotopes derived from DA and MTX were in the same range, their distribution patterns were consistently different. The results demonstrate that intracerebrally microperfused drugs may have quantitatively different spatial distributions, related to their physicochemical characteristics and/or their binding and metabolism in brain tissue.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002945:Cisplatin / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006892:Hydroxydopamines / Q000378:metabolism; D008727:Methotrexate / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D051381:Rats
D006892:Hydroxydopamines; D002945:Cisplatin; D000983:Antipyrine; D004298:Dopamine; D009638:Norepinephrine; D008727:Methotrexate