Mcn a 343

Temsirolimus, everolimus, apomorphine HCl, GR73632, SR141716A, thapsigargin, and FPL64176 were purchased from Tocris (Minneapolis, MN). Ridaforolimus and rapamycin were acquired from MedChemExpress and Calbiochem, respectively. Quinpirole HCl, serotonin HCl (5-HT), 2-methyl-serotonin maleate salt (2-methyl-5-HT), pilocarpine HCL, McN-A-343, and cisplatin (cis-platinum (II) diamine dichloride (Pt (NH₃)₂)Cl₂) were obtained from Sigma/RBI. Apomorphine, quinpirole, serotonin, 2-methy-5-HT, McN-A-343, GR73632, pilocarpine, and cisplatin were dissolved in distilled water. thapsigargin was dissolved in 10% DMSO (Sigma) in water. mTOR inhibitors and FPL64176 were dissolved in DMSO and then diluted with three volumes of distilled water to a final DMSO concentration of 25%. SR141716A was dissolved in a 1:1:18 solution of ethanol, emulphor (EL-620, a polyoxyethylated vegetable oil, GAF Corporation, Linden, NJ), and 0.9% saline. All drugs were administered at a volume of 0.1 ml/10 g of body weight. The doses and routes used for the emetogens were based upon previous publications from our laboratory (Darmani et al., 2019 (link); Darmani et al., 2020 (link); Zhong and Darmani 2020 (link)).

Muscarinic agonists arecoline, carbachol furmethide, iperoxo, McN-A343, N-desmethylclozapine, oxotremorine, pilocarpine (Sigma, St.Louis, MO, USA), xanomeline (Tocris Bioscience, Bristol, UK), JR-6, and JR-7 (synthesized at Barry University, Miami Shores, FL, USA [19 (link)]) were used in this study. Structures of all used agonists are in the Supplementary Material (Figure S2).

The following drugs were used in the present study: clonidine, dexmedetomidine, yohimbine, GR73632, SR141716A, FPL64176, thapsigargin, and ZD7288 were purchased from Tocris (Minneapolis, MN, USA); McN-A-343, quinpirole HCl, and rolipram were purchased from Sigma-Aldrich (St. Louis, MO, USA); 2-methyl-serotonin maleate salt (2-Methyl-5-HT) was purchased from Santa Cruz Biotechnology (Dallas, TX, USA). SR141716A was dissolved to twice the stated drug dose in a 1:1:18 solution of ethanol:Emulphor™:0.9% saline and was then diluted further with an equal volume of saline. FPL64176 was dissolved in 25% DMSO in water. thapsigargin was dissolved in 10% DMSO in distilled water. Other drugs were dissolved in distilled water. All drugs were administered at a volume of 0.1 mL/10 g of body weight. The doses and routes used for the emetogens were based upon previous publications from our laboratory [6 (link),43 (link),87 (link)].