[Abstract Title]. - Society for Neuroscience

Authors: *E. M. ADKINS 1,3 , M. D. SMITH 1 , G. BULAJ 2 , H. S. WHITE 1 ;
1 Pharmacol. and Toxicology, 2 Medicinal Chem., Univ. of Utah, Salt Lake City, UT;
3 NeuroAdjuvants, Inc., Salt Lake City, UT
Abstract: The neuropeptide galanin displays antinociceptive activity upon both direct injection
into the brain as well as intrathecal delivery (Gu, et al., Behav. Brain Res., 179:331, 2007;
Xiong, et al., Regul. Pept. 132:85, 2005). However, neither of these routes of delivery are
feasible in humans. Furthermore, galanin displays low permeability through the blood-brainbarrier
(BBB) as well as low metabolic stability (~5 min half-life in plasma). Here we describe a
modified galanin analog, NAX 5055, that is centrally localized and exhibits antinociceptive
activity in multiple rodent models of pain when administered systemically. NAX 5055 is a
rationally designed analog of the truncated galanin neuropeptide that contains lipoamino acid and
basic residues at the C-terminus. NAX 5055 was chemically synthesized and purified via HPLC.
The antinociceptive effects of NAX 5055 were evaluated in the formalin test in both male CF-1
mice and male Sprague-Dawley rats. For formalin tests, NAX 5055 or vehicle was administered
i.p. to animals at the time-to-peak effect (1 hour) before hindlimb plantar injection of 20 µl of
5% (mice) or 50 µl of 2.5% (rats) v/v formalin. Animals were observed for flinching behavior
and the total area under the curve (AUC) and the percent of control AUC were calculated. NAX
5055 displayed potent antinociceptive activity in both the mouse and rat formalin tests. At 1.5
mg/kg (mice), and 0.5 mg/kg (rats), flinching decreased (p< 0.01) in the acute phase by 54% and
64% and in the inflammatory phase by 74% and 64%, respectively. The ability of NAX 5055 (1
mg/kg, i.p.) to attenuate mechanical allodynia in the rat partial sciatic nerve ligation model was
evaluated using the von Frey test (Seltzer et al., Pain. 43: 205, 1990). NAX 5055 (2 mg/kg, i.p.)
elevated the paw withdrawal threshold (507 + 123% of predrug, p