TAN-452

TAN-452 is an orally active, selective peripherally acting δ-opioid receptor (DOR) antagonist with a Ki of 0.47 nM and a Kb of 0.21 nM. TAN-452 is an antagonist for μ-opioid receptor (MOR; Ki=36.56 nM and Kb=9.43 nM) and κ-opioid receptor (KOR; Ki=5.31 nM and Kb=7.18 nM). TAN-452, a derivative of Naltrindole, demonstrates low brain penetrability and attenuates morphine-induced side effects without affecting pain control[1].

Signaling Pathways >> GPCR/G Protein >> Opioid Receptor

Signaling Pathways >> Neuronal Signaling >> Opioid Receptor

Research Areas >> Neurological Disease

Ki: 0.47 nM (DOR), 36.56 nM (MOR) and 5.31 nM (KOR)[1] Kb: 0.21 nM (DOR), 9.43 nM (MOR) and 7.18 nM (KOR)[1]

TAN-452 (1, 3, 10 mg/kg for p.o. or 0.3, 1, 3 mg/kg for s.c.) suppresses morphine-induced emesis in ferrets[1]. TAN-452 (30 mg/kg/2 mL for PO or 3 mg/kg/mL for IV) has a T1/2 of 2.1 hours[1]. TAN-452 suppresses morphine-induced small intestinal transit (SIT) inhibition in a dose-dependent manner. Administration of TAN-452 at 30 mg/kg alone does not affect SIT[1]. TAN-452 (10, 30 mg/kg; s.c.) significantly suppresses morphine-induced antinociception 30 min after administration. TAN-452 (po) produces no effect up to 300 mg/kg[1]. Animal Model: Male ferrets (1.3-1.9 kg)[1] Dosage: 1, 3, 10 mg/kg (p.o.) or 0.3, 1, 3 mg/kg (s.c.) Administration: PO or SC; before morphine Result: Prevented morphine-induced emesis in half of the animals with orally administered of 1 mg/kg and completely abolished emesis at 3 and 10 mg/kg. Completely abolished emesis by subcutaneous injection at 0.3, 1, and 3 mg/kg. Animal Model: Crj:CD(SD) IGS male rats (7 weeks old)[1] Dosage: 30 mg/kg/2 mL for PO or 3 mg/kg/mL for IV (Pharmacokinetic Analysis) Administration: Orally or intravenously Result: Had a T1/2 of 2.1 hours, a CL of 78.1 mL/min•kg, a Vss of 12.1 L/kg, and a Cmax of 526 ng/mL.

[1]. Tsutomu Suzuki, et al. Pharmacological profile of TAN-452, a novel peripherally acting opioid receptor antagonist for the treatment of opioid-induced bowel syndromes. Life Sci. 2018 Dec 15;215:246-252.