The following selective Sig-1R ligands were used: PRE-084 at a dose of 0.25 mg/kg (0589,TOCRIS; Bristol, UK), EST79232 and EST79376 at doses of 0.5 and 5 mg/kg (synthesized and supplied by ESTEVE Pharmaceuticals). The compounds were dissolved in 0.5% hydroxypropyl-methylcellulose (HPMC;
H7509, Sigma-Aldrich) in distilled water and were administered by intraperitoneal (i.p.) route twice daily (bid) in a volume of 10 mL/kg. Administrations were given from 30 min after rhizotomy surgery until 42 days post-injury (dpi), the end of the study; in the SOD1
G93A study, treatments were given from 8 to 16 weeks of age (see
Figure 6).
For the spinal nerve injury (rhizotomy, rhizo), female WT mice were distributed in the following experimental groups: uninjured control (CTL) (
n = 16), rhizo + vehicle 0.5% HPMC (
n = 14), rhizo + PRE-084 0.25 mg/kg (
n = 5), rhizo + EST79232 0.5 mg/kg (
n = 5), rhizo + EST79232 5 mg/kg (
n = 6), rhizo + EST79376 0.5 mg/kg (
n = 5), rhizo + EST79376 5 mg/kg (
n = 5). For the SOD1
G93A studies, male transgenic mice were divided into 4 groups: SOD1+ vehicle 0.5% HPMC (
n = 13), SOD1 + PRE-084 0.25 mg/kg (
n = 5), SOD1 + EST79232 5 mg/kg (
n = 7), SOD1+ EST79376 5 mg/kg (
n = 6), with B6SJL male WT age-matched mice used as negative control of the disease (
n = 13).
Gaja-Capdevila N., Hernández N., Yeste S., Reinoso R.F., Burgueño J., Montero A., Merlos M., Vela J.M., Herrando-Grabulosa M, & Navarro X. (2022). EST79232 and EST79376, Two Novel Sigma-1 Receptor Ligands, Exert Neuroprotection on Models of Motoneuron Degeneration. International Journal of Molecular Sciences, 23(12), 6737.