Antinociceptive, Antiallodynic and Antihyperalgesic Effects of the 5-HT 1A Receptor Selective Agonist, NLX-112 in Mouse Models of Pain

Neuropharmacology. 2017 Oct;125:181-188. doi: 10.1016/j.neuropharm.2017.07.022. Epub 2017 Jul 24.


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-HT1A 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: NLX-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.

Keywords: Befiradol (PubChem CID: 9865384); Chemotherapy-induced peripheral neuropathy; Formalin (PubChem CID: 712); NLX-112; Oxaliplatin (PubChem CID: 9887054); Pain models; Painful diabetic neuropathy; Streptozotocin (PubChem CID: 29327); Tactile allodynia; Thermal hyperalgesia; WAY100635 (PubChem CID: 5684).

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Antineoplastic Agents / toxicity
  • Cyclohexanes / pharmacology
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Formaldehyde
  • Hot Temperature
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Male
  • Mice
  • Motor Activity / drug effects
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Nociceptive Pain / drug therapy*
  • Nociceptive Pain / metabolism
  • Organoplatinum Compounds / toxicity
  • Oxaliplatin
  • Piperazines / pharmacology
  • Piperidines / pharmacology*
  • Pyridines / pharmacology*
  • Random Allocation
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin 5-HT1 Receptor Agonists / pharmacology*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology
  • Streptozocin
  • Touch


  • Analgesics
  • Antineoplastic Agents
  • Cyclohexanes
  • Organoplatinum Compounds
  • Piperazines
  • Piperidines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • WAY 101363
  • Oxaliplatin
  • Receptor, Serotonin, 5-HT1A
  • Formaldehyde
  • Streptozocin
  • befiradol