Antinociceptive, antiallodynic and antihyperalgesic effects of the 5-HT1A, receptor selective agonist, NLX-112 in mouse models of pain

作者：Salat Kinga^*; Kolaczkowski Marcin; Furgala Anna; Rojek Adriana; Sniecikowska Joanna; Varney Mark A; Newman Tancredi Adrian

来源：Neuropharmacology, 2017, 125: 181-188.

DOI：10.1016/j.neuropharm.2017.07.022

• Pain models
• NLX-112
• Tactile allodynia
• Thermal hyperalgesia
• Painful diabetic neuropathy
• Chemotherapy-induced peripheral neuropathy

Background and purpose:: NLX-112 (a.k.a. befiradol, F13640) is a drug candidate intended for the treatment of L-DOPA-induced dyskinesia. It is a highly selective serotonin 5-HT1A, receptor full agonist which has been previously tested in a variety of models of CNS effects including analgesic activity in rat. Its activity in mouse models of pain has not been previously investigated.
Experimental approach: The activity of NLX-112 was tested in mouse models of acute pain (hot plate), tonic pain (intraplantar formalin test), in the oxaliplatin-induced neuropathic pain model of chemotherapy-induced peripheral neuropathy and in the streptozotocin (STZ)-induced model of painful diabetic neuropathy.
Key results: The main findings indicate that (i) NLX-112 was markedly active in the formalin test with potent reduction of paw licking in both phases of the test (minimal effective dose (MED) 0.5 mg/kg i.p. and p.o. in acute phase, and 0.1 mg/kg i.p. and 1 mg/kg p.o. in late phase). The effects of NLX-112 in this test were completely abolished by the selective 5-1-1T(1A) receptor antagonist, WAY100635; (ii) NLX-112 was active in the hot plate test and in the oxaliplatin-induced neuropathic pain model of chemotherapy-induced peripheral neuropathy, but at markedly higher doses (MED 2.5 mg/kg i.p.); (iii) NLX-112 was least active in the STZ-induced model of painful diabetic neuropathy (MED 5 mg/kg i.p.); (iv) NLX-112 did not affect locomotor activity.
Conclusions and implications: NIX-112 may have significant potential for treatment of tonic pain but may be less promising as a candidate for treatment of chemotherapy-induced or diabetic neuropathic pain.

• 出版日期2017-10