Irl 1620

Ketamine (Henry Schein Animal Health, Dublin, OH, USA) was administered at a dose of 100 mg/kg, intraperitoneally (i.p.), and xylazine (Lloyd Laboratories, Shenandoah, IA, USA) was administered at a dose of 10 mg/kg, i.p. IRL-1620 [N-Succinyl-[Glu9, Ala11,15] endothelin 1] (Bachem Americas, Inc., Torrance, CA 90505) was dissolved in isotonic saline and administered at a dose of 5 µg/kg, intravenously (i.v.) via tail vein at 2, 4 and 6 h post MCAO. The dose of IRL-1620 was based on our previous studies^{20 (link)–22 (link)} and Phase I safety and tolerability studies^{23 (link)}.

Anesthesia drugs: Ketamine (Henry Schein Animal Health, Dublin, OH, USA) at a dose of 100 mg/kg and xylazine (Lloyd Laboratories, Shenandoah, IA, USA) at a dose of 10 mg/kg were administered intraperitoneally (i.p.).
Study drugs: IRL-1620 (N-Succinyl-[Glu9, Ala 11,15] endothelin 1) (Bachem Americas, Inc., Torrance, CA, USA) was dissolved in isotonic saline and administered at a dose of 5 mcg/kg intravenously (i.v.) via tail vein at 2, 4, and 6 h post MCAO. BQ788 (American Peptide Co, Inc., Sunnyvale, CA, USA) was dissolved in isotonic saline and administered at a dose of 1 mg/kg i.v., 15 min prior to initial administration of either vehicle or IRL-1620 in Groups IV and V, respectively. The doses of both IRL-1620 and BQ788 were based on our preliminary studies (12 (link), 13 (link)).

Morphine sulfate, 7,8-didehydro-4,5α-epoy-17-methylmorphinan-3,6α-diol sulfate, (Sigma-Aldrich, St. Louis, MO, USA), was dissolved in sterile saline and injected subcutaneously (s.c.). Oxycodone hydrochloride, 4,5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride (Sigma-Aldrich, St. Louis, MO, USA), was dissolved in sterile saline and injected subcutaneously (s.c.). Selective ET_B receptor agonist, IRL-1620, (N-Succinyl-[Glu9, Ala11,15]-endothelin 1; Bachem Americas, Inc., Torrance, CA 90505), was dissolved in sterile saline and injected intravenously (i.v.) through the tail vein.