Effect of prazosin on norepinephrine concentration and turnover in rat brain and heart.
Prazosin hydrochloride injected i.p. into rats markedly increased MOPEG sulfate (3-methoxy-4-hydroxy-phenylethylene glycol sulfate) concentration in brain and the rate of MOPEG sulfate accumulation after probenecid. The increase in MOPEG sulfate was dose-related over a 5-40 mg/kg dose range. After a 20 mg/kg dose of prazosin, the increase in MOPEG sulfate was greater than after the same dose of phenoxybenzamine and persisted for up to 24 hr. The rate of metaraminol disappearance from rat brain after alpha-methyl-m-tyrosine injection and the decline in brain norepinephrine after inhibition of its synthesis by alpha-methyltyrosine injection were increased in rats pretreated with prazosin. These findings indicate that prazosin increased brain norepinephrine turnover, probably via compensation to central alpha adrenoceptor blockade. Prazosin increased sertonin and 5-hydroxy-indoleacetic acid concentration and slightly decreased 3,4-dihydroxy-phenylacetic acid in rat brain. Although prazosin had little effect on brain norepinephrine concentration, heart norepinephrine was depleted for up to 16 hr after a 20 mg/kg dose of prazosin, and the depletion at 4 hr was dose-related down to 2 mg/kg of prazosin. These biochemical changes may all result from prazosin's block of alpha adrenergic receptors.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D008297:Male; D008680:Metaraminol / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats
D011799:Quinazolines; D010643:Phenoxybenzamine; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D008680:Metaraminol; D009638:Norepinephrine; D011224:Prazosin