Characteristics of analgesia induced by noncatecholic phenylethylamine derivatives: Possible involvement of endogenous opioid peptides and serotonin in phenylethylamine analog-induced analgesia.

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Characteristics of the analgesic action of phenylethylamine derivatives, amphetamine, phenylethylamine (PEA), hydroxyphenylethylamine (OHPEA) and hydroxyphenylalanine (OHF), were examined. Pain threshold of mice was measured by using the hot plate method. OHPEA (50 mg/kg), amphetamine (0.5-8 mg/kg) or PEA (50 mg/kg) produced an analgesic effect in the absence of MAO inhibitor, and the analgesia was reversed by naloxone (5 mg/kg) or reserpine (2 mg/kg×2). Ten mg/kg of PEA, 250 mg/kg of OHF and 10 mg/kg of OHPEA could not produce detectable analgesia, but they revealed analgesic activity when mice were pretreated with pargyline (100 mg/kg). Analgesia induced by a combined use of PEA, OHF or OHPEA with pargyline was inhibited by naloxone or p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis. Amphetamine-induced analgesia was also blocked by PCPA. Analgesia induced by PEA or OHPEA was blocked by methysergide (2 mg/kg). From the above findings, it was concluded that PEA, OHPEA, OHF and amphetamine possess similar characteristics in their analgesic action, and their analgesic actions involve the participation of endogenous serotonin and endogenous opioid peptides.
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