Male guinea pigs (300–350 g) were housed under standard conditions with a 12 h light-dark cycle and free access to food and water. Animals were euthanized by pentobarbital sodium overdose. [1]
- Trachea were rapidly removed, placed in Krebs-Henseleit (KH) solution (composition: NaCl 119 mM, NaHCO₃ 25 mM, CaCl₂ 2.5 mM, KCl 4.7 mM, KH₂PO₄ 1.2 mM, MgSO₄ 1.2 mM, glucose 11.1 mM, indomethacin 5 × 10⁻⁶ M). Cartilaginous rings were opened longitudinally and mounted in 20 mL organ baths at 37.4°C, continuously bubbled with 95% O₂/5% CO₂ (pH 7.4). Preparations were preloaded with 5 mN and equilibrated for ≥1 h, washed every 20 min. [1]
- Relaxation protocol: Tracheal rings were precontracted with histamine (3 × 10⁻⁶ M), methacholine (5 × 10⁻⁷ M), or KCl (20 mM). After stabilization, cumulative concentrations of drotaverine were added. Full relaxation was achieved with 2.5 mM EGTA, considered 100% relaxation. [1]
- Inhibition of contraction protocol: After control contractions with constrictor agents, the lowest concentration of drotaverine was added and incubated for 15 min, then constrictor was administered. This was repeated with increasing concentrations. [1]
- Isometric contractile responses were measured using force displacement transducers and a computer-aided data acquisition system. [1]

Absorption, Distribution and Excretion
Drapaverin hydrochloride is not completely absorbed after oral administration, and its bioavailability varies greatly among individuals. After a single oral dose of 80 mg, the absolute bioavailability ranges from 24.5% to 91%, with a mean of 58.2 ± 18.2%. The mean Cmax is 292 ± 88 ng/mL. The mean AUC is 3251 ± 950 ngh/mL. The mean Tmax is 1.9 ± 0.54 hours. Drapaverin hydrochloride is primarily metabolized and excreted via the liver. Approximately 67% of the drug is excreted in feces, and 20% in urine. The mean volume of distribution after a single oral dose of 80 mg is 193 ± 48 L. The mean volume of distribution after an intravenous injection of 80 mg is 195 ± 48 L.
After a single oral dose of 80 mg, the mean renal clearance was 0.59 ± 0.18 mL/min. After intravenous administration of 80 mg, the mean renal clearance was 0.73 ± 0.29 mL/min.
Metabolism/Metabolites

Drapaverine hydrochloride has been reported to be primarily metabolized in the liver, which is its main clearance pathway. It may also be excreted in the bile as conjugated metabolites. The proposed metabolic pathways and metabolites are based on limited animal studies: In rats, the major metabolites of drapaverine identified are 4'-deethyldrapaverine, 6-deethyldrapaverine, drapaveridone, and 4'-deethyldrapaveridone, all of which are excreted in the bile as glucuronidated forms. 4'-Deethyldrapaveridone is the most important metabolite excreted in the bile.
Biological Half-Life

After a single oral dose of 80 mg, the mean half-life is 9.11 ± 1.29 hours. Following intravenous administration of 80 mg, the mean half-life was 9.33 ± 1.02 hours.

Protein Binding
(No relevant information available.)

[1]. Patai Z, Guttman A, Mikus EG. Assessment of the Airway Smooth Muscle Relaxant Effect of Drotaverine. Pharmacology. 2018;101(3-4):163-169.

Dapivirine hydrochloride belongs to the isoquinoline class of drugs. Dapivirine hydrochloride is an antispasmodic drug whose mechanism of action is through inhibition of phosphodiesterase-4 (PDE4). It is a benzylisoquinoline derivative structurally related to papaverine, but its antispasmodic activity is stronger. Dapivirine hydrochloride has been used to treat various spastic disorders, such as gastrointestinal diseases, biliary motility disorders, and vasomotor disorders associated with smooth muscle spasms. It has also been used to treat dysmenorrhea, miscarriage, and induced labor. In recent years, Dapivirine hydrochloride has also attracted attention for the treatment of benign prostatic hyperplasia, parainfluenza virus, and avian influenza virus. Dapivirine hydrochloride has not yet been approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), or Health Canada. It is approved for use in Thailand in oral tablet or intramuscular injection form.
Drug Indications
Dapivirine hydrochloride is used to relieve smooth muscle spasms of the gastrointestinal and genitourinary systems, such as cholecystitis and gallbladder disease.





Mechanism of Action Drotaverine hydrochloride is a selective inhibitor of phosphodiesterase 4 (PDE4), an enzyme responsible for degrading cyclic adenosine monophosphate (cAMP). Inhibition of PDE4 leads to elevated cAMP levels, resulting in smooth muscle relaxation. Recent studies have shown that low levels of cAMP are associated with the development of brain tumors, thus the possibility of PDE4 inhibitors as potential anticancer drugs has been investigated. Pharmacodynamics Drotaverine hydrochloride is an antispasmodic with a smooth muscle relaxant effect. It can relieve visceral spasms and promote cervical dilation. In vitro experiments have shown that drotaverine hydrochloride has inhibitory effects on various human tumor cell lines and non-malignant mouse fibroblasts. Drotaverine hydrochloride may have a mild allosteric calcium channel blocking effect: in vitro experiments have shown that the action of drotaverine hydrochloride is similar to that of voltage-dependent L-type calcium channel blockers.

C24H31NO4.HCL

433.96818

433.201

985-12-6

Drotaverine-d10 hydrochloride

1712095

White to light yellow solid powder

1.097 g/cm3

564ºC at 760 mmHg

208-212ºC

240.7ºC

6.056

1

5

9

29

511

0

CCOC1=CC=C(/C=C\2/C3=C(CCN2)C=C(C(=C3)OCC)OCC)C=C1OCC.Cl

OMFNSKIUKYOYRG-MOSHPQCFSA-N

InChI=1S/C24H31NO4/c1-5-26-21-10-9-17(14-22(21)27-6-2)13-20-19-16-24(29-8-4)23(28-7-3)15-18(19)11-12-25-20/h9-10,13-16,25H,5-8,11-12H2,1-4H3/b20-13-

(1Z)-1-[(3,4-diethoxyphenyl)methylidene]-6,7-diethoxy-3,4-dihydro-2H-isoquinoline

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~230.43 mM)
DMSO : ~62.5 mg/mL (~144.02 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)