Absorption, Distribution and Excretion
Imidazole reached peak plasma levels within 15 to 30 minutes in rats dosed with approximately 17 mg/kg bw and disappeared within 4 hours. Similar results were obtained for imidazole with ITF 182, a novel drug called Selezen that consists of the salt of protonated imidazole and 2-hydroxybenzoate in 1:1 molar quantities, with doses containing up to 66 mg imidazole/kg bw. The pharmacokinetic parameters were determined in human studies with ITF 182 in single (248 mg of imidazole) and multiple dose (3 single doses per day) studies. The pharmacokinetic parameters were comparable between different experiments, i.e. single or multiple dosing, oral or rectal applications, or oral tablet or oral drops did not exert marked influences. The main pharmacokinetic parameters in humans after oral intake may be summarized as follows: maximum plasma levels were reached after approximately 3 hours, elimination half-life was approximately 1.8 to 3 hours. Bioavailability was complete. Protein binding was determined to range between 5 to 15 %. In contrast, no effects were noted in a pilot study after dermal application.

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Metabolism / Metabolites
Response of enzymes involved in liver drug metabolism to imidazole treatment was determined in several studies. No increase in total microsomal P450 content was observed after a 4 day i.p. administration of 200 mg/kg bw per day in female Sprague-Dawley rats. Statistically significantly increased activities of 7-ethoxycoumarin-O-deethylase (1.7-fold) and Aminopyrine-N-demethylase (1.26-fold) were noted whereas aniline and p-nitrophenol hydroxylases were insignificantly reduced. New Zealand White rabbits treated with imidazole (200 mg/kg bw, 4 days) showed increased total p450-content in liver (1.24-fold) compared with controls and a 4.47-fold increase of the isozyme 3a. No significant changes were noted in pretreated Syrian Hamsters of both sexes (200 mg/kg bw, 4 days) with respect to relative liver weight, total microsomal p450-content, microsomal and cytosolic enzyme activities involved in phase I (demethylation of p-nitroanisole and ethylmorphine, NADPH-Cytochrome C-reductase) and phase II drug metabolism (sulfotransferase, glutathione transferase).

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Biological Half-Life
... Elimination half-life /in humans/ was approximately 1.8 to 3 hours.

Toxicity Summary
IDENTIFICATION AND USE: Imidazole, an organic alkaloid, is an important pharmacophore in drug discovery. Imidazole is used as a Karl Fischer reagent in analytical chemistry and a reagent in synthetic organic chemistry. It is also used in the biological control of pests, especially fabric-feeding insects, often in combination with dl-p-fluorophenylalanine. HUMAN STUDIES: Autophagic events are induced by imidazole in HEC-1B cells. Accumulation of autophagic vacuoles in imidazole-treated cells was verified by conversion of LC3 protein, as well as confocal and transmission electron microscopy. Furthermore, imidazole blocked autophagic degradation by impairing maturation of autophagosomes into autolysosomes. Concurrently, imidazole treatment induced apoptosis in HEC-1B cells, accompanied by activation of caspase 9 and 3. The proapoptotic effect was mediated by increased Bim expression. Moreover, imidazole upregulated the protein level of FoxO3a and induced its increased nuclear localization. In addition, siRNA-mediated silencing of FoxO3a effectively attenuated imidazole-induced Bim upregulation and cell death, indicating direct involvement of this pathway in the imidazole-induced apoptosis. ANIMAL STUDIES: When 80% Imidazole was applied to the intact rabbit skin as an aqueous paste for 1 or 4 hours under occlusive dressing skin reactions were noted as early as one hour after removal of the dressing. Focal necrosis developed overnight in all animals and was described as leather-like at the end of the observation period. The application of 0.1 g of unchanged imidazole to the rabbit's eye (Draize test) affected conjunctiva, cornea, and the nictating membrane of the animals. In rats, the symptoms of acute oral exposure were described as convulsions and disequilibria with lateral posture. Deaths occurred within one day. Apathy and accelerated respiration was noted in survivors. Imidazole was given daily by gavage to rats at 20, 60, and 180 mg/kg bodyweight per day. Liver and the male kidney were identified as target organs in the animal groups receiving 180 mg/kg bw per day as substantiated by significantly increased relative liver weights in males and females which correlated with minimal to slight centrilobular liver cell hypertrophy in males and females, and by a significant increase of absolute and relative kidney weight in high-dose males that was accompanied by an accumulation of alpha2u-microglobulin in the epithelia and lumina of the proximal tubules of the male rat renal cortex. No changes of the male and female reproductive organs including sperm quality were noted in a rat 3-month study. In a developmental study in rats, the incidence of external malformations (anasarca and/or cleft palate) was significantly increased. About 10% of the high dose fetuses (180 mg/kg) were affected while no such changes were observed in the control. Skeletal malformations were also statistically significantly increased: 7.8% affected fetuses per litter were noted in the high dose group compared to 1.1% in the control. The incidences of shortened scapula, bent radius, bent ulna, malpositioned and bipartite sternebrae were statistically significantly increased. Soft tissue variations (dilated renal pelvis and ureter) were significantly increased in fetuses from high dose dams compared to controls (27% vs. 6.4%). The incidences of skeletal variations, mainly delays of the ossification process, were statistically significantly increased from 91% in the control group to 98.4% in the high dose group. Imidazole was not mutagenic when tested with Salmonella typhimurium TA 1535, TA 100, TA 1537, and TA 98 both in the presence and absence of metabolic activation.

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Non-Human Toxicity Values
LD50 Rat oral 960-970 mg/kg bw
LD50 Mouse (male) oral 1180 mg/kg bw
LD50 Rat oral 220 mg/kg
LD50 Rat sc 626 mg/kg
For more Non-Human Toxicity Values (Complete) data for Imidazole (10 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 which has the migrating hydrogen at position 1. It is a conjugate base of an imidazolium cation. It is a conjugate acid of an imidazolide. It is a tautomer of a 4H-imidazole.
Imidazole has been reported in Lens culinaris and Homo sapiens with data 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.)