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

Abstract

Abstract-Characteristicsof 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/kgx2). 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).

Uliginosin B, a natural phloroglucinol derivative, presents a multimediated antinociceptive effect in mice

“…Altogether, results here described and previous ones suggest that uliginosin B has a pharmacological profile that resembles tramadol, which activates opioid pathways and is able to inhibit the monoamine reuptake [28–30]. Moreover, several authors emphasize the role of descending serotoninergic pathways on the central antinociceptive and antihyperalgesic effects of paracetamol[31] and the importance of the interaction between serotoninergic and opioidergic neurotransmissions in the antinociceptive actions of morphine[32,33] and fluoxetin,[34] as well as in the hyponociceptive effect induced by swimming in rodents [35]…”

Characteristics of Antinociception Induced by Noncatecholic Phenylethylamine Derivatives: The Relation of Endogenous Norepinephrine to Phenylethylamine Analog-Induced Antinociception

“…These results suggest that PEA derivatives may release norepinephrine in the CNS. It has been demonstrated that antinocicep tive action by PEA derivatives may involve endogenous serotonin and endogenous opioid peptides (5). Besides these mecha nisms, the above findings in the present study suggests the following: PEA derivatives may induce the release of norepinephrine in the CNS, and then the released norepinephrine may also produce an antinociception.…”

“…Amphetamine, one of the noncatecholic phenylethylamine derivatives, has been well-known to produce a slight but significant antinociceptive action (4). We (5) have also reported that PEA derivatives such as PEA, OHPEA and amphetamine have antinociceptive actions, and the actions involve the participation of endogenous serotonin and endogenous opioid peptides.…”

2S,3R 3-Amino-2-hydroxy-4-phenylbutanoic acid derivatives, enkephalinase inhibitors, augment met5-enkephalin-induced antinociception.

“…The hot plate was main tained at a temperature of 55.5 to 56.0°C by using a thermistor. For the purpose of deter ming the pain threshold of mice or the latency, the length of time required for mice placed on the hot plate to initiate any one of the fol lowing behaviors: jumping or shaking, licking, holding or lifting their paws was measured in a room kept at 24±1 °C and at 55±5% relative humidity and protected from external noise (13). The cut-off time was set at 25 sec in order to protect mice from burning their paws.…”