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

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

Author information

1
Chair of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9 St., 30-688 Krakow, Poland. Electronic address: kinga.salat@uj.edu.pl.
2
Chair of Pharmaceutical Chemistry, Jagiellonian University, Medical College, Medyczna 9 St., 30-688 Krakow, Poland.
3
Chair of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9 St., 30-688 Krakow, Poland.
4
Neurolixis Inc., 34145 Pacific Coast Highway #504, Dana Point, CA 92629, USA.

Abstract

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)

[Indexed for MEDLINE]

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