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Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in ra

Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in ra

  1. helikophis
    This study investigated the effects of chlorpheniramine (CPA, 10–25
    mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and
    pyrilamine (PYRI, 20 mg/kg) on 3,4-methylenedioxymethamphetamine (MDMA, 20
    mg/kg 2)-induced hyperthermia and depletion of indoles in rat brains, on the uptake of
    serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic
    amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free
    radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP,
    PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h
    apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly
    following the drug injections for 13 h. As compared to saline controls, MDMA increased
    body temperature and decreased levels of indoles, measured by HPLC, in several brain
    regions of rats. CPA attenuated and DIPH had no effect on MDMA-induced hyperther-
    mia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated
    these effects. CPA inhibited the binding of [3H]paroxetine and [3H]nisoxetine to the
    synaptosomes of cerebral cortex and of [3H]win 35,428 to the synaptosomes of striatum.
    CPA, DIPH, TRIP, and PYRI inhibited [3H]serotonin uptake. CPA, PYRI, and TRIP, but
    not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the
    antihistamines on MDMA-induced hyperthermia and depletion of serotonin are dis-
    cussed.