EFFECT OF PRAZOSIN ON NOREPINEPHRINE CONCENTRATION AND TURNOVER IN RAT-BRAIN AND HEART

  • 1 January 1978
    • journal article
    • research article
    • Vol. 231  (1) , 30-41
Abstract
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 h. 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 nonepinephrine turnover, probably via compensation to central .alpha.-adrenoreceptor blockade. Prazosin increased serotonin and 5-hydroxyindoleacetic acid concentration and slightly decreased 3,4-dihydroxyphenylacetic acid in rat brain. Although prazosin had little effect on brain norepinephrine concentration, heart norepinephrine was depleted for up to 16 h after a 20 mg/kg dose of prazosin. The depletion at 4 h was dose-related down to 2 mg/kg of prazosin. These biochemical changes may all result from prazosin''s block of .alpha.-adrenergic receptors.