Naltrindole (hydrochloride)

111469-81-9

C26H27ClN2O3

DMSO : >= 188 mg/mL (416.89 mM)

GPCR/G Protein; Neuronal Signaling

Naltrindole hydrochloride is a highly potent and selective non-peptide delta opioid receptor antagonist with a K_i of 0.02 nM. IC50 & Target: Ki: 0.02 nM (delta opioid), 64 nM (u opioid), 66 nM (kappa opioid)^[1] In Vitro: Opioid drugs exert a wide spectrum of physiological and behavioral effects. These effects are mediated via membrane-bound receptors, of which the best characterized are the kappa, delta, and mu receptors^[1]. Naltrindole inhibits the proliferation of cultured human U266 MM cells in a time- and dose-dependent manner with an EC₅₀ of 16 uM. Treatment of U266 cells with naltrindole significantly decreases the level of the active, phosphorylated form of the kinases, extracellular signal-regulated kinase and Akt, which may be related to its antiproliferative activity^[2]. Naltrindole inhibits growth and induces apoptosis in the three characteristic SCLC cell lines, NCI-H69, NCI-H345, and NCI-H510. Naltrindole treatment reduces constitutive phosphorylation of Akt/PKB on serine 473 and threonine 308 in cells and also its downstream effectors glycogen synthase kinase-3beta and the Forkhead transcription factors AFX and FKHR^[3]. In Vivo: Naltrindole significantly decreases tumor cell volumes in human MM cell xenografts in severe combined immunodeficient mice^[2]. In mice, naltrindole at 20 mg/kg s.c. antagonizes the delta-selective agonist effect of [D- Ser, Leu, Thr]enkephalin (DSLET) without blocking the antinociceptive effect of morphine or U50488H. Naltrindole is the only highly selective delta antagonist that is active upon peripheral administration^[4]. Acute naltrindole induces significant decreases in external and total ambulation (horizontal activity) and rearing behaviour (vertical activity), as well as a significant increase in grooming frequency. In animals chronically treated with naltrindole there is an increase in total ambulation one day after the discontinuation of the treatment^[5].