The anticonvulsant neuropeptide galanin is a potent regulator of neuronal excitability, and has a well established role in pain modulation, making it a potential target for novel therapies. The authors designed peripherally-acting galanin analogs that exhibit preferential binding towards GalR2 over GalR1 galanin receptors. For the present work, preclinical analgesic and safety studies were conducted with a monodisperse oligoethylene glycol (dPEG)–containing galanin analog, NAX 409-9 (previously reported as GalR2-dPEG24). NAX 409-9 increased the paw withdrawal threshold to mechanical stimulation following partial sciatic nerve ligation in rats (2 mg/kg). Conversely, NAX 409-9 had no effect in the tail flick or hot plate assays, and did not negatively affect gastrointestinal motility, respiratory rate, or bleed time. These studies illustrate that this nonbrain-penetrating galanin analog reduces pain behaviors in several models, and does not produce some of the dose-limiting toxicities associated with other analgesics.
See article at J Pharmacol Exp Ther 2015, 352:185–193.
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