Naltrindole hydrochloride

Naltrindole hydrochloride is a highly potent and selective non-peptide δ opioid receptor antagonist with a Ki of 0.02 nM.
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 μM. 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-3β and the Forkhead transcription factors AFX and FKHR[3].
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 δ-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 δ 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].
Reference:
[1]. Raynor K, et al. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4.
[2]. Mundra JJ, et al. Naltrindole inhibits human multiple myeloma cell proliferation in vitro and in a murine xenograft model in vivo. J Pharmacol Exp Ther. 2012 Aug;342(2):273-87.
[3]. Chen YL, et al. Inhibition of akt/protein kinase B signaling by naltrindole in small cell lung cancer cells.
[4]. Portoghese PS, et al. Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist. Eur J Pharmacol. 1988 Jan 27;146(1):185-6.
[5]. Fernández B, et al. Postnatal naltrindole treatments induce behavioural modifications in preweanling rats. Neurosci Lett. 2000 Mar 31;283(1):73-6.