Programa de Pós Graduação em Bioquímica e Bioprospecção (PPGBBio), Grupo de Pesquisa em Neurobiotecnologia, GPN, Universidade Federal de Pelotas, UFPEL, Pelotas, RS, Brazil.
Laboratório de Síntese Orgânica Limpa (LASOL), Universidade Federal de Pelotas, UFPEL, Pelotas, RS, Brazil.
Pharmacol Rep. 2017 Oct;69(5):871-877. doi: 10.1016/j.pharep.2017.03.016. Epub 2017 Mar 27.
This study evaluated the antinociceptive action of α-(phenylalanyl) acetophenone (PSAP) in mice.
Evaluated whether the serotonergic, adrenergic and dopaminergic systems are involved in PSAP antinociceptive activity. PSAP was administered intragastrically (ig) 30min prior to formalin or glutamate test and compared with a standard drug, meloxicam (10mg/kg, ig).
The treatment with PSAP (10-50mg/kg) caused inhibition in the neurogenic phase and reduced the paw oedema caused by intraplantar (ipl) injection of formalin. PSAP (1-50mg/kg) decreased the nociceptive response in the inflammatory phase of the formalin test and in licking behaviour triggered by glutamate at doses of 0.1-50mg/kg. The antinociceptive effect of PSAP (1mg/kg) was abolished when the animals were pre-treated with prazosin (α-adrenergic antagonist receptor, 0.15mg/kg, intraperitoneally, ip), yohimbine (α-adrenergic antagonist receptor, 1mg/kg, ip) and sulpiride (D/D dopamine antagonist, 5mg/kg, ip). The antinociceptive effect of PSAP (1mg/kg) was not abolished by WAY100635 (5-HT-selective serotoninergic antagonist, 0.7mg/kg, ip), ketanserin (selective antagonist of serotonergic 5-HT, 0.3mg/kg, ip), ondansetron (5-HT selective serotoninergic antagonist, 0.5mg/kg, ip) or SCH23390 (D dopamine receptor antagonist, 0.05mg/kg, ip) in the glutamate test. No changes in locomotor activity were observed in the animals treated with PSAP and/or antagonists in the open field test.
These results showed the antinociceptive action of PSAP in formalin and glutamate tests and the involvement of the dopaminergic and adrenergic systems in its antinociceptive activity.
本研究评估了 α-（苯丙氨酰基）苯乙酮（PSAP）在小鼠中的镇痛作用。
评估了 5-羟色胺能、肾上腺素能和多巴胺能系统是否参与 PSAP 的镇痛活性。PSAP 于福马林或谷氨酸测试前 30 分钟经胃内给药（ig），并与标准药物美洛昔康（10mg/kg，ig）进行比较。
PSAP（10-50mg/kg）治疗可抑制神经源性阶段，并减少足底内（ipl）注射福马林引起的足肿胀。PSAP（1-50mg/kg）可减少福马林测试炎症阶段的疼痛反应和谷氨酸引起的舔舐行为，剂量为 0.1-50mg/kg。当动物预先用哌唑嗪（α-肾上腺素能拮抗剂受体，0.15mg/kg，腹腔内，ip）、育亨宾（α-肾上腺素能拮抗剂受体，1mg/kg，ip）和舒必利（D/D 多巴胺拮抗剂，5mg/kg，ip）预处理时，PSAP（1mg/kg）的镇痛作用被消除。PSAP（1mg/kg）的镇痛作用不受 WAY100635（5-HT 选择性 5-羟色胺能拮抗剂，0.7mg/kg，ip）、酮色林（5-HT 选择性 5-羟色胺能拮抗剂，0.3mg/kg，ip）、昂丹司琼（5-HT 选择性 5-羟色胺能拮抗剂，0.5mg/kg，ip）或 SCH23390（D 多巴胺受体拮抗剂，0.05mg/kg，ip）的影响，在谷氨酸测试中。在开放场测试中，用 PSAP 和/或拮抗剂处理的动物未观察到运动活动的变化。
这些结果表明 PSAP 在福马林和谷氨酸测试中的镇痛作用以及多巴胺能和肾上腺素能系统在其镇痛活性中的参与。
