Absorption, Distribution and Excretion
Following administration of imidazole to rats at a dose of approximately 17 mg/kg body weight, peak plasma concentrations were reached within 15 to 30 minutes and disappeared within 4 hours. Similar results were obtained with ITF 182 (a novel drug called Selezen, composed of a salt of protonated imidazole and 2-hydroxybenzoate in a 1:1 molar ratio) at doses up to 66 mg/kg body weight. In human studies, pharmacokinetic parameters of ITF 182 were determined through single-dose (248 mg imidazole) and multiple-dose (three times daily) studies. Pharmacokinetic parameters were comparable between different experiments, i.e., single or multiple administration, oral or rectal administration, and oral tablets or oral drops did not have a significant effect. Following oral administration, the main pharmacokinetic parameters in humans can be summarized as follows: peak plasma concentrations were reached approximately 3 hours later, and the elimination half-life was approximately 1.8 to 3 hours. Bioavailability was 100%. Protein binding was determined to be 5% to 15%. In contrast, a preliminary study showed no effect observed after transdermal administration. Multiple studies have determined the response of enzymes involved in hepatic drug metabolism to imidazole treatment. In female Sprague-Dawley rats, no increase in total microsomal P450 content was observed after intraperitoneal injection of 200 mg/kg body weight/day for 4 consecutive days. Statistical analysis showed significantly increased activities of 7-ethoxycoumarin-O-deethylase (1.7-fold) and aminopyrine-N-demethylase (1.26-fold), while the activities of aniline and p-nitrophenol hydroxylase were not significantly decreased. In New Zealand white rabbits treated with imidazole (200 mg/kg body weight, 4 days), the total p450 content in the liver increased by 1.24-fold compared to the control group, and the content of isoenzyme 3a increased by 4.47-fold. No significant changes were observed in the relative liver weight, total microsomal p450 content, or microsomal and cytoplasmic enzyme activities involved in phase I (demethylation of p-nitroanisole and ethylmorphine, NADPH-cytochrome C reductase) and phase II drug metabolism (sulfonyltransferase, glutathione transferase) in Syrian hamsters (both male and female) pretreated with imidazole (200 mg/kg body weight, 4 days).

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Biological half-life
...In humans, the elimination half-life is approximately 1.8 to 3 hours.

Toxicity Summary
Identification and Uses: Imidazole is an organic alkaloid and an important pharmacophore in drug discovery. It is used as a Karl Fischer reagent in analytical chemistry and as a reagent in synthetic organic chemistry. It is also used for the biocontrol of pests, particularly fabric-feeding insects, often in combination with dl-p-fluorophenylalanine. Human Studies: Imidazole induces autophagy in HEC-1B cells. The accumulation of autophagosomes in imidazole-treated cells was confirmed by LC3 protein transformation and confocal and transmission electron microscopy. Furthermore, imidazole blocks autophagic degradation by inhibiting the maturation of autophagosomes into autolysosomes. Simultaneously, imidazole treatment induces apoptosis in HEC-1B cells, accompanied by activation of caspase 9 and caspase 3. This pro-apoptotic effect is mediated by increased Bim expression. In addition, imidazole upregulates FoxO3a protein levels and induces increased nuclear localization. Furthermore, siRNA-mediated FoxO3a silencing effectively attenuated imidazole-induced Bim upregulation and cell death, indicating that this pathway is directly involved in imidazole-induced apoptosis. Animal experiments: An 80% imidazole aqueous paste was applied to intact rabbit skin for 1 or 4 hours and then bandaged with a occlusive dressing. Skin reactions were observed as early as 1 hour after dressing removal. Focal necrosis appeared in all animals overnight and was described as leathery changes at the end of the observation period. Instillation of 0.1 g of unaltered imidazole into the rabbit eye (Draize test) affected the conjunctiva, cornea, and nictitating membrane. In rats, acute oral exposure manifested as convulsions and balance disorders accompanied by a lateral recumbent posture. All rats died within one day. Surviving rats exhibited lethargy and rapid breathing. Rats were administered imidazole daily by gavage at doses of 20, 60, and 180 mg/kg body weight. In the group receiving a daily dose of 180 mg/kg body weight, the liver and male kidneys were identified as target organs. This conclusion is supported by the following evidence: a significant increase in the relative weight of the liver in both male and female animals, which was associated with slight hypertrophy of the central lobular cells in both male and female livers; and a significant increase in both absolute and relative kidney weight in male animals in the high-dose group, accompanied by the accumulation of α2u-microglobulin in the proximal tubular epithelium and lumen of the renal cortex in male rats. A 3-month rat study did not observe any changes in male and female reproductive organs (including sperm quality). In a rat developmental study, the incidence of external malformations (generalized edema and/or cleft palate) was significantly increased. Approximately 10% of fetuses in the high-dose group (180 mg/kg) were affected, while no such changes were observed in the control group. The incidence of skeletal malformations was also significantly increased: 7.8% of fetuses in the high-dose group were affected, compared to 1.1% in the control group. The incidence of scapular shortening, radius curvature, ulnar curvature, abnormal sternal position, and sternal bifurcation were all significantly increased. Compared with the control group, the incidence of soft tissue variations (dilatation of the renal pelvis and ureter) in fetuses born to mothers in the high-dose group was also significantly increased (27% vs. 6.4%). The incidence of skeletal variations (mainly delayed ossification) was also significantly increased, from 91% in the control group to 98.4% in the high-dose group. Imidazole was not mutagenic to Salmonella Typhimurium TA 1535, TA 100, TA 1537, and TA 98, regardless of metabolic activation.

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Non-human toxicity values
Oral LD50 in rats: 960-970 mg/kg body weight
Oral LD50 in male mice: 1180 mg/kg body weight
Oral LD50 in rats: 220 mg/kg
Subcutaneous LD50 in rats: 626 mg/kg
For more complete data on the non-human toxicity values of imidazole (10 values in total), please visit the HSDB record page.

[1]. In vitro and in silico screening of 2, 4, 5-trisubstituted imidazole derivatives as potential xanthine oxidase and acetylcholinesterase inhibitors, antioxidant, and antiproliferative agents. Applied Sciences, 2020, 10(8): 2889.

[2]. Design and synthesis of diphenyl-1H-imidazole analogs targeting Mpro/3CLpro enzyme of SARS-CoV-2. Medicinal Chemistry Research, 2024 June 26, 1554-8120.

[3]. Imidazole: a selective inhibitor of thromboxane synthetase. Prostaglandins. 1977 Apr;13(4):611-8.

1H-Imidazole is an imidazole tautomer with its migrating hydrogen at the 1-position. It is the conjugate base of the imidazoleonium cation, the conjugate acid of imidazole compounds, and also the tautomer of 4H-imidazole. Imidazole has been reported to exist in lentils and the human body, and relevant data are available.

C3H4N2

68.0773

68.037

288-32-4

82370-43-2;227760-40-9;1467-16-9 (mono-hydrochloride);5587-42-8 (hydrochloride salt)

795

White to off-white solid powder

1.1±0.1 g/cm3

257.0±9.0 °C at 760 mmHg

88-91 °C(lit.)

145.0±0.0 °C

0.0±0.5 mmHg at 25°C

1.528

-0.16

1

1

0

5

28.1

0

RAXXELZNTBOGNW-UHFFFAOYSA-N

InChI=1S/C3H4N2/c1-2-5-3-4-1/h1-3H,(H,4,5)

1H-imidazole

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 (~1468.86 mM)
DMSO : ~100 mg/mL (~1468.86 mM)

Solubility in Formulation 1: 100 mg/mL (1468.86 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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