Promethazine hydrochloride

Clonidine hydrochloride (C7897; Sigma), Amitriptyline hydrochloride (A8404; Sigma), HC-30031 (TRPA1 antagonist; H4415; Sigma), Gabapentin (G154; Sigma), A-803467 (Nav1.8 blocker; 2976; Tocris), TC-N1752 (Nav1.7 blocker; 4435; Tocris), Atenolol (A7655; Sigma), Ibuprofen (I4883;Sigma), Naloxone (0599; R&D Systems) Atenolol (A7655; Sigma), Lamotrigine (L3791; Sigma), Enalipril (CDS020548; Aldrich), Ethyl 3-aminobenzoate methanesulfonate (Tricaine; E10521; Sigma), Omeprazole (O104; Sigma), Promethazine hydrochloride (P4651: Sigma), Diphenhydramine hydrochloride (D3630; Sigma), and Pancuronium bromide (P1918; Sigma) were dissolved in DMSO to a 1000x concentration. Buprenorphine hydrochloride (12496–0757; Reckitt Benckiser Pharmaceuticals) was obtained as a 3mg/mL injection solution from UW Medicine Drug Services. Candidate analgesics were further diluted in a solution of EM and 2% DMSO for the behavioral assay.

Itraconazole, milbemycin oxime, ibuprofen, farnesol, haloperidol, promethazine hydrochloride, and curcumin were purchased from Sigma-Aldrich (Buchs, Switzerland). Voriconazole (Vfend IV 200 mg) was acquired from Pfizer (Zurich, Switzerland). Milbemycin oxime and ibuprofen were dissolved in ethanol and distilled water (dH₂O), respectively, at a concentration of 5 mg/ml. The other compounds were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich) to constitute stock solutions (5 mg/ml or 0.5 mg/ml for less soluble compounds). Stock solutions were stored at –20°C until use. Etest strips containing Itraconazole (reference [Ref.] Etest, 0.002 to 32 μg/ml) and voriconazole (Ref. Etest, 0.002 to 32 μg/ml) were acquired from bioMérieux SA (Geneva, Switzerland) and stored at 4°C until use. Nonimpregnated cellulose disks (bioMérieux) were used for the diffusion assays.

For work involving parasites, chlorpheniramine maleate salt, chlorpromazine hydrochloride, desipramine hydrochloride, promethazine hydrochloride, verapamil hydrochloride and CQ diphosphate (all from Sigma-Aldrich) were dissolved in PBS to a working concentration of 1 mM. LynxTag-CQ_GREEN (BioLynx Technologies, Singapore; hereafter abbreviated to ‘CQ_GREEN’) was dissolved in DMSO to the same concentration. All compounds were stored at −20°C and protected from light. For microsome uptake assays, methiothepin mesylate salt, metergoline, loperamide hydrochloride, octoclothepin maleate salt, mibefradil dihydrochloride hydrate, L703,606 oxalate salt hydrate, and chlorprothixene hydrochloride (all from Sigma-Aldrich) were dissolved in DMSO to 10 mM and stored at 4°C. verapamil hydrochloride, adenosine triphosphate (ATP), and CQ diphosphate (all from Sigma-Aldrich) were dissolved in water to 7.5 mM, 50 mM and 0.1 M respectively and stored at −20°C. Tritiated CQ (³H-CQ; from Moravek Biochemicals and Radiochemicals) was diluted in water to 5.32 µM and stored at −20°C; specific activity was 4.7 Ci/mmol.