Dithiazanine iodide targets intestinal parasites, particularly nematodes. The compound's mechanism of action is believed to involve the irreversible inhibition of glucose uptake in parasites, leading to energy depletion and death. Dithiazanine iodide also inhibits the aerobic metabolism and glycolysis of intestinal worms. The compound induces irreversible relaxation and death of Trichuris trichiura. The exact molecular target is not well-defined.

In vitro, Dithiazanine iodide has been shown to be effective against various intestinal parasites. It induces irreversible relaxation and death of Trichuris trichiura in vitro. The compound inhibits glucose uptake and glycolysis in parasites. Dithiazanine iodide's anthelmintic activity has been demonstrated against Trichuris, Strongyloides, Ascaris, Enterobius, and hookworms. The compound's activity is concentration-dependent.

In vivo, Dithiazanine iodide has been shown to be effective in clearing intestinal nematode infections in dogs and other animals. It is used in veterinary medicine for the treatment of trichuriasis, strongyloidiasis, ascariasis, enterobiasis, and hookworm infections. The compound clears circulating microfilariae from the blood, although the exact mechanism is not fully understood. They evidently lose motility, become trapped in capillary beds, and are eventually phagocytized by host cells.

In vitro anthelmintic assays for Dithiazanine iodide typically involve exposing parasites to various concentrations of the compound and assessing motility and viability over time. The compound is dissolved in an appropriate solvent and added to the culture medium containing the parasites. The EC50 (concentration required to inhibit 50% of parasite motility or viability) is determined from dose-response curves. The effect of Dithiazanine iodide on glucose uptake and glycolysis in parasites can also be studied.

In vitro cell-based studies with Dithiazanine iodide are limited, as the compound is primarily used as an anthelmintic rather than a drug for mammalian cells. However, its effects on mammalian cells can be studied to assess its toxicity. Cells are treated with Dithiazanine iodide at various concentrations, and cell viability is assessed using MTT or similar assays. The compound's effect on cellular metabolism and mitochondrial function can also be evaluated.

In vivo animal studies with Dithiazanine iodide are typically conducted in dogs or other animals infected with intestinal nematodes. The compound is administered orally. The reduction in fecal egg counts or parasite burden is assessed. The compound's safety and tolerability in animals are also evaluated. Pharmacokinetic studies are performed to measure Dithiazanine iodide levels in blood and tissues.

Absorption, Distribution and Excretion
This blue-purple compound is absorbed in very small amounts in the intestines, but enough to give tissues a pale blue hue. Because most of the drug is not absorbed, the dog's feces and vomit are blue-green to purple.
The pharmacokinetic properties of Dithiazanine iodide have been studied in animals. Following oral administration, the compound is poorly absorbed from the gastrointestinal tract, which is desirable for an intestinal anthelmintic. The compound is excreted in the feces. Detailed PK parameters such as half-life, Cmax, and AUC have not been extensively reported. The compound is typically stored under recommended conditions.

Non-Human Toxicity Values
Oral LD50 in rats: 165-192 mg/kg Oral LD50 in mice: 4-16 mg/kg
The toxicity of Dithiazanine iodide has been evaluated in animals. The compound has a relatively low toxicity in mammals when used at recommended doses. However, Dithiazanine iodide can cause adverse effects, including gastrointestinal upset, vomiting, and diarrhea. Overdose can lead to more severe effects. Appropriate safety precautions should be taken when handling the compound. Dithiazanine iodide is for veterinary use only and is not approved for use in humans.

[1]. Dithiazanine, an effective broad-spectrum anthelmintic; results of therapy of trichuriasis, strongyloidiasis, enterobiasis, ascariasis, and hookworm infection. J Am Med Assoc. 1957 Dec 21;165(16):2063-7.

[2]. A FATALITY ASSOCIATED WITH DITHIAZANINE IODIDE THERAPY. JAMA. 1965 Apr 26;192:326-7.

Dithiazanine iodide appears as green needle-like crystals. It is used as a veterinary anthelmintic, a photographic emulsion sensitizer, and an insecticide. It is not registered as an insecticide in the United States (EPA, 1998).
3-Ethyl-2-(5-(3-ethyl-2-benzothiazolinyl)-1,3-pentadienyl)benzothiazolium. A benzothiazolium compound, formerly used as an antinematode, currently used as a fluorescent dye.
See also: Dithiazanine iodide (preferred); Dithiazanine (with active moiety); Dithiazanine iodide; Piperazine citrate (component).

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Mechanism of Action
The mechanism by which Dithiazanines clear circulating microfilariae from the blood is unclear. They apparently lose motility, remain in the capillary bed, and are eventually phagocytosed by host cells… The mechanism of action of Dithiazanine drugs on worms has not been fully elucidated. Studies on canine whipworms have shown that this drug irreversibly inhibits glucose absorption, thereby significantly reducing free glucose levels and leading to the depletion of energy-rich phosphate bonds. It is unclear whether these physiological changes also occur in heartworm microfilariae exposed to this drug.

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Therapeutic Use
Drug (Veterinary): Dithiazanine has broad-spectrum anthelmintic activity, effective not only against heartworm microfilariae but also against common canine intestinal nematodes (hookworms, roundworms, whipworms), strongyloides stercoralis, and possibly canine spiralworms.
Drug (Veterinary): Dithiazanine should be administered orally immediately after or during feeding.
Drug (Veterinary): As vomiting and diarrhea are common side effects, the lowest daily dose (6.6-11 mg/kg) is recommended for 7 days. Dividing the daily dose into two 3.3 mg/kg doses administered with feeding may help reduce the occurrence of side effects. If microfilariae are still detected in the animal's blood after 7 days, the dose may be increased to 11 mg/kg daily until the blood microfilariae test is negative or no more than 10 days later.
Deworming medication (nematodes)
Drug Warnings
This product is considered a toxic deworming medication.
...Vomiting and diarrhea are common side effects...
A small number of dogs have died within 3 days after receiving a dose of 20 mg/kg/day. These dogs may have developed liver and kidney disease because Dithiazanine is toxic to both the liver and kidneys.
Dithiazanine iodide is a broad-spectrum anthelmintic used primarily in veterinary medicine. It is effective against a range of intestinal nematodes, including Trichuris, Strongyloides, Ascaris, Enterobius, and hookworms. Dithiazanine iodide is also a cyanine dye. The compound is not approved for use in humans. Dithiazanine iodide is an important tool for the control of intestinal parasites in dogs and other animals.

C23H23N2S2+.I-

518.47612

518.035

514-73-8

7187-55-5;CAS# 514-73-8 (iodide);

6433197

Green to dark green solid powder

249ºC

1.491

2.58

0

4

5

28

537

0

CCN\1C2=CC=CC=C2S/C1=C/C=C/C=C/C3=[N+](C4=CC=CC=C4S3)CC.[I-]

MNQDKWZEUULFPX-UHFFFAOYSA-M

InChI=1S/C23H23N2S2.HI/c1-3-24-18-12-8-10-14-20(18)26-22(24)16-6-5-7-17-23-25(4-2)19-13-9-11-15-21(19)27-23;/h5-17H,3-4H2,1-2H3;1H/q+1;/p-1

(2E)-3-ethyl-2-[(2E,4E)-5-(3-ethyl-1,3-benzothiazol-3-ium-2-yl)penta-2,4-dienylidene]-1,3-benzothiazole;iodide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~16.67 mg/mL (~32.15 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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