RB 101 hydrochloride is a blood-brain barrier-crossing prodrug as well as aminopeptidase N and neutral endopeptidase-24.11 inhibitor. RB 101 hydrochloride blocks enkephalin breakdown, elevates extracellular enkephalin levels and activate δ-opioid receptor and dopamine D1 receptor. RB 101 hydrochloride can be used for the research of pain, depressive syndromes, and diabetic neuropathy [1] [2] [3].
In Vivo, RB 101 (2.5-40 mg/kg; i.v.; single administration) hydrochloride dose-dependently inhibits [3H]diprenorphine binding to mouse brain opioid receptors under basal conditions[1]. RB 101 (5-20 mg/kg; i.v.; single administration) hydrochloride potentiates stress-induced analgesia in mice, reaching 85% analgesia at 5 mg/kg when combined with warm-water swim stress[1]. RB 101 (1.25-10 mg/kg; i.v.; single slow injection) hydrochloride induces a dose-dependent, long-lasting increase in spontaneous motor activity in mice via δ opioid and dopamine D1 receptor stimulation[2]. RB 101 (2.5-10 mg/kg; i.v.; single slow injection) hydrochloride dose-dependently attenuates conditioned suppression of motility in shocked mice and increases striatal dopamine turnover, via δ opioid and dopamine D1 receptor stimulation[2]. RB 101 (2.5-10 mg/kg; i.v.; single slow injection (20 s); 10 min before testing) hydrochloride significantly reduces immobility time in the mouse forced swim test via δ opioid and dopamine D1 receptor stimulation[2]. RB 101 (5-40 mg/kg; i.v.) hydrochloride produces dose-dependent, μ- and δ-opioid receptor-mediated antinociception in Streptozocin -induced diabetic rats with neuropathic pain, completely suppressing mechanical hyperalgesia at doses of 20 and 40 mg/kg i.v.[3].
In Vitro, RB 101 hydrochloride enhances spontaneous methionine-enkephalin-like material outflow from rat spinal cord tissue via inhibition of enkephalin degrading enzymes[1].
References:
[1]. Ruiz-Gayo M, et al. In vivo occupation of mouse brain opioid receptors by endogenous enkephalins: blockade of enkephalin degrading enzymes by RB 101 inhibits [3H]diprenorphine binding. Brain Res. 1992;571(2):306-312.
[2]. Baamonde A, et al. Antidepressant-type effects of endogenous enkephalins protected by systemic RB 101 are mediated by opioid delta and dopamine D1 receptor stimulation. Eur J Pharmacol. 1992;216(2):157-166.
[3]. Coudoré-Civiale MA, et al. Enhancement of the effects of a complete inhibitor of enkephalin-catabolizing enzymes, RB 101, by a cholecystokinin-B receptor antagonist in diabetic rats. Br J Pharmacol. 2001;133(1):179-185.
In Vivo, RB 101 (2.5-40 mg/kg; i.v.; single administration) hydrochloride dose-dependently inhibits [3H]diprenorphine binding to mouse brain opioid receptors under basal conditions[1]. RB 101 (5-20 mg/kg; i.v.; single administration) hydrochloride potentiates stress-induced analgesia in mice, reaching 85% analgesia at 5 mg/kg when combined with warm-water swim stress[1]. RB 101 (1.25-10 mg/kg; i.v.; single slow injection) hydrochloride induces a dose-dependent, long-lasting increase in spontaneous motor activity in mice via δ opioid and dopamine D1 receptor stimulation[2]. RB 101 (2.5-10 mg/kg; i.v.; single slow injection) hydrochloride dose-dependently attenuates conditioned suppression of motility in shocked mice and increases striatal dopamine turnover, via δ opioid and dopamine D1 receptor stimulation[2]. RB 101 (2.5-10 mg/kg; i.v.; single slow injection (20 s); 10 min before testing) hydrochloride significantly reduces immobility time in the mouse forced swim test via δ opioid and dopamine D1 receptor stimulation[2]. RB 101 (5-40 mg/kg; i.v.) hydrochloride produces dose-dependent, μ- and δ-opioid receptor-mediated antinociception in Streptozocin -induced diabetic rats with neuropathic pain, completely suppressing mechanical hyperalgesia at doses of 20 and 40 mg/kg i.v.[3].
In Vitro, RB 101 hydrochloride enhances spontaneous methionine-enkephalin-like material outflow from rat spinal cord tissue via inhibition of enkephalin degrading enzymes[1].
References:
[1]. Ruiz-Gayo M, et al. In vivo occupation of mouse brain opioid receptors by endogenous enkephalins: blockade of enkephalin degrading enzymes by RB 101 inhibits [3H]diprenorphine binding. Brain Res. 1992;571(2):306-312.
[2]. Baamonde A, et al. Antidepressant-type effects of endogenous enkephalins protected by systemic RB 101 are mediated by opioid delta and dopamine D1 receptor stimulation. Eur J Pharmacol. 1992;216(2):157-166.
[3]. Coudoré-Civiale MA, et al. Enhancement of the effects of a complete inhibitor of enkephalin-catabolizing enzymes, RB 101, by a cholecystokinin-B receptor antagonist in diabetic rats. Br J Pharmacol. 2001;133(1):179-185.