Mitragynine pseudoindoxyl 

Mitragynine pseudoindoxyl is a potent orally active agonist of the μ-opioid receptor (MOR-1, K_i=0.8 nM) and an antagonist of the δ-opioid receptor (DOR-1, K_i=3.0 nM). Mitragynine pseudoindoxyl has moderate affinity for the κ-opioid receptor (KOR-1, K_i=24 nM) and does not recruit β-arrestin-2, acting through G protein-mediated signaling pathways without β-arrestin-2-related activation. Mitragynine pseudoindoxyl produces potent analgesic activity through a mixed μ-agonist/δ-antagonist mechanism, with low side effects such as physical dependence, respiratory depression, and constipation, and no rewarding or aversive behaviors. Mitragynine pseudoindoxyl reduces hyperactivity, inhibits GI transit, and enhances characteristics, making it a potential analgesic^[1][2].

Mitragynine pseudoindoxyl (25°C, 90 min) exhibits high affinity for CHO cells expressing murine MOR-1, DOR-1, and KOR-1, with the strongest affinity for MOR-1 and DOR-1. The Ki values ??are MOR-1: 0.8±0.2 nM, DOR-1: 3.0±1.3 nM, and KOR-1: 24±0.9 nM^[1].
Mitragynine pseudoindoxyl (30°C, 60 min) is a potent full agonist of MOR-1 and an antagonist of DOR-1 and KOR-1 in opioid receptor-transfected CHO cells. It effectively stimulates^[35S]GTPγS binding and does not recruit β-arrestin-2^[1].
Mitragynine pseudoindoxyl (100 pM-30 nM; 20 min) inhibits electrically stimulated contractions of guinea pig ileum in a concentration-dependent manner, with a pD2 value of 8.96±0.09. Its potency is 100 times that of mitragynine and 20 times that of morphine. This effect can be antagonized by Naloxone (HY-17417A)^[2].
Mitragynine pseudoindoxyl (1 nM-1 μM) inhibits electrically stimulated contractions of mouse vas deferens in a concentration-dependent manner, with a pD2 value of 7.40. This effect can be antagonized by Naltrexone (HY-76711) and Naloxone (HY-17417A)^[2].
Mitragynine pseudoindoxyl (10 μM, in combination with 10 μM DAMGO; 90 min) does not recruit β-arrestin-2 in CHO cells expressing modified MOR-1, and it antagonizes DAMGO (HY-P0210)-induced β-arrestin-2 recruitment in a concentration-dependent manner, with an IC₅₀ value of 34 nM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Mitragynine pseudoindoxyl (0.38 μg; intracerebroventricular injection; single dose), (0.76 mg/kg; subcutaneous injection; single dose), and (7.5 mg/kg; oral administration; single dose) produced potent analgesic effects in the hot plate/radiant heat tail-flick analgesia model in CD1, C57BL/6, and 129Sv6 male mice across multiple mouse strains and different routes of administration, with subcutaneous injection showing the strongest effect. The half-maximal effective doses (ED₅₀) were 0.38 μg (intracerebroventricular injection), 0.76 mg/kg (subcutaneous injection), and 7.5 mg/kg (oral administration)^[1].
Mitragynine pseudoindoxyl (1.5 mg/kg; subcutaneous injection; twice daily; 29 days) showed slow development of analgesic tolerance in the analgesic tolerance model in CD1 male mice, with a 6-fold ED₅₀ shift only appearing after 29 days^[1].
Mitragynine pseudoindoxyl (1.5 mg/kg; subcutaneous injection; single dose) and (4 mg/kg; subcutaneous injection; single dose) inhibited gastrointestinal transit in the gastrointestinal transit model in CD1 male mice, but reached a plateau at 4 mg/kg, with no further inhibition^[1].
Mitragynine pseudoindoxyl (1.3 mg/kg; intraperitoneal injection; once daily; 2 days) and (3.2 mg/kg; intraperitoneal injection; once daily; 2 days) showed no conditioned place preference or aversion in the conditioned place preference/aversion model in CD1 male mice^[1].
Mitragynine pseudoindoxyl (1.5 mg/kg; subcutaneous injection; single dose) in the antisense oligonucleotide receptor downregulation analgesia model in CD1 male mice, targeting MOR-1 exon 1 with antisense oligonucleotides (5-10 μg, intracerebroventricular injection, administered on days 1, 3, and 5), significantly reduced its analgesic effect, while DOR-1... Treatment with the KOR-1 antisense oligonucleotide had no effect, confirming that the analgesia is dependent on the MOR-1 receptor^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

414.49

C₂₃H₃₀N₂O₅

2035457-43-1

Solid

Off-white to pink

O=C1[C@@]2(NC3=CC=CC(OC)=C31)[C@@]4([H])N(C[C@H]([C@H](C4)/C(C(OC)=O)=C\OC)CC)CC2

Room temperature in continental US; may vary elsewhere.

• [1]. Váradi A, et al. Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2. J Med Chem. 2016 Sep 22;59(18):8381-97.  [Content Brief]

  [2]. Yamamoto LT, et al. Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa. Gen Pharmacol. 1999 Jul;33(1):73-81.  [Content Brief]