Mitragynine pseudoindoxyl

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].