NAX 810-2

NAX 810-2 was designed to overcome the central limitation of the GalR1-preferring galanin analog NAX-5055, namely on-target hyperglycemia. By biasing affinity toward galanin receptor 2, the developers aimed to keep the anticonvulsant and analgesic activity mediated by GalR2 while removing the insulinostatic effect associated with GalR1. NAX 810-2 possesses about fifteen-fold greater affinity for GalR2 than GalR1 and functionally activates GalR2 at therapeutic concentrations ^[1].

As an anticonvulsant, NAX 810-2 dose-dependently blocked seizures after intravenous administration in the corneal kindling model of partial epilepsy and in the 6 Hz model of pharmacoresistant epilepsy, with a median effective dose in the sub-milligram-per-kilogram range, a time to peak effect near thirty minutes, a plasma half-life of about 1.2 hours, and linear pharmacokinetics ^[1]. As an analgesic it was active across a broad battery: it raised paw-withdrawal latency after carrageenan, attenuated both phases of the formalin response, reduced tail-flick and plantar-incision pain, and lessened mechanical allodynia in the partial sciatic nerve ligation model of neuropathic pain ^[2].

The decisive advantage over NAX-5055 was metabolic. At doses that were analgesic, NAX 810-2 did not impair insulin secretion acutely or after repeated dosing, and it did not raise growth hormone levels, confirming that shifting selectivity toward GalR2 uncouples the therapeutic effects from the endocrine liability ^[2]. The design work that produced GalR2-preferring analogs from the GalR1-preferring backbone, including N-terminal truncation and N-methylation strategies, was reported alongside these efficacy studies ^[3]. NAX 810-2 stands as the leading GalR2-biased galanin analog and a proof that subtype selectivity can separate benefit from adverse effect in the galanin system.

In preclinical testing NAX 810-2 displayed a favorable profile: at anticonvulsant and analgesic doses it did not impair insulin secretion or elevate growth hormone, addressing the main liability of its GalR1-preferring predecessor. Motor impairment appeared at the higher end of the anticonvulsant dose range, with an effective dose roughly half that impairing dose, indicating a workable but finite therapeutic window. Human safety has not been established. General peptide-therapeutic considerations, such as parenteral administration and potential immunogenicity, apply and remain unstudied clinically.

NAX 810-2 emerged around 2017 from the University of Utah and NeuroAdjuvants program led by Cameron Metcalf, Brian Klein, Grzegorz Bulaj, and H. Steve White, as the GalR2-preferring answer to NAX-5055's hyperglycemia problem. It was reported in back-to-back studies establishing its anticonvulsant pharmacokinetics and its analgesic and safety profile, positioning it as a first-in-class galanin-based analgesic and antiseizure candidate.

NAX 810-2 is well regarded in the galanin and epilepsy literature as the compound that demonstrated GalR2 selectivity could retain efficacy while shedding the metabolic liability of GalR1 agonism. It is cited as the most advanced GalR2-preferring galanin analog and as a template for neuropeptide analgesics. It has no consumer or nootropic presence and remains investigational.