Fuller R W, Snoddy H D, Perry K W
Arch Int Pharmacodyn Ther. 1978 Jan;231(1):30-41.
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.
腹腔注射盐酸哌唑嗪可显著提高大鼠脑中硫酸3-甲氧基-4-羟基苯乙二醇（MOPEG硫酸盐）的浓度以及丙磺舒给药后MOPEG硫酸盐的积累速率。在5-40mg/kg的剂量范围内，MOPEG硫酸盐的增加与剂量相关。给予20mg/kg剂量的哌唑嗪后，MOPEG硫酸盐的增加幅度大于相同剂量的酚苄明，且持续长达24小时。预先用哌唑嗪处理的大鼠，在注射α-甲基-m-酪氨酸后间羟胺从大鼠脑中消失的速率以及注射α-甲基酪氨酸抑制其合成后脑去甲肾上腺素的下降幅度均增加。这些发现表明，哌唑嗪可能通过对中枢α肾上腺素能受体阻断的代偿作用增加了脑内去甲肾上腺素的周转率。哌唑嗪增加了大鼠脑中血清素和5-羟基吲哚乙酸的浓度，并使3,4-二羟基苯乙酸略有降低。尽管哌唑嗪对脑内去甲肾上腺素浓度影响不大，但给予20mg/kg剂量的哌唑嗪后，心脏去甲肾上腺素在长达16小时内减少，且4小时时的减少与剂量相关，低至2mg/kg的哌唑嗪。这些生化变化可能均由哌唑嗪对α肾上腺素能受体的阻断引起。
