Milbemycin oxime Chemical Properties

Melting point:

169.6-177.4°

Flash point:

412℃

storage temp. 

Store at -20°C

solubility 

DMSO:100.0(Max Conc. mg/mL);91.13(Max Conc. mM)

form 

A crystalline solid

Stability:

Hygroscopic

InChIKey

LKMMLHTWKLEARD-MGZQXKBQSA-N

Safety Information

RIDADR 

2588

WGK Germany 

3

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

2932206000

Toxicity

LD50 orally in mice: 1000-1500 mg/kg (Ciba-Geigy)

Milbemycin oxime Usage And Synthesis

Description

Milbemycin is an oral medication used as a dewormer and heartworm preventive. This medication should not be used in doses higher than the recommended heartworm prevention dose, except under veterinary supervision. Studies support the safety of milbemycin products in Collies and other breeds prone to the MDR-1 gene mutation when used at the recommended heartworm prevention dose.

Uses

Milbemycin Oxime is active against a broad spectrum of nematodes, although it is less potent against heartworms than ivermectin. Its miticide spectrum includes Sarcoptes and Demodex. The USA FDA approval for milbemycin oxime as formulated alone does not indicate insecticidal activity. The substance is often combined with other parasiticides to achieve a broader spectrum of action. Such products include: Milbemax (with praziquantel) Sentinel Flavor Tabs (with lufenuron) Recently the drug has been used in marine reef aquaria to control parasitic harptacoid copepod (Tegastidae) infestations on captive hard coral colonies. It is an effective full tank treatment for these parasites because it is not toxic to corals in the dosage required to kill the parasites. Shrimps, crabs and other crustaceans should be removed prior to treatment, as they will be killed by the treatment.

Drug Interactions

Milbemycin should not used in combination with cyclosporine, quinidine or ketoconazole.

Uses

Intestinal parasite deworming in dogs and for heartworm prevention in dogs and cats.

Mechanism of action

Like avermectins, milbemycins are products of fermentation by Streptomyces species. They have a similar mechanism of action, but a longer half-life than the avermectins. Milbemycin Oxime is produced by Streptomyces hygroscopicus aureolacrimosus. It opens glutamate sensitive chloride channels in neurons and myocytes of invertebrates, leading to hyperpolarisation of these cells and blocking of signal transfer.

Side Effects

The drug is tolerated well, even by dogs with multiple drug resistance. In high doses, it can cause side effects like stupor, tremor and ataxia.

Uses

Milbemycin oxime is a semi-synthetic macrocyclic lactone prepared by the oxidation and oximation of a mixture of two natural products, milbemycin A3 and A4 (in ~30:70 ratio). Milbemycin oxime is used therapeutically for the prevention of intestinal parasites in dogs. Like the other milbemycin/avermectins, it was developed for intestinal parasite control in animals and acts by opening glutamate sensitive chloride channels in neurons of invertebrates leading to paralysis by hyperpolarisation of these cells and signal transfer blocking.

Uses

controls intestinal parasites in animals

Clinical Use

Milbemycin oxime (Milbemycin) is available as an oral chewable tablet (2.3–27 mg) for heartworm prevention in dogs and cats, as well as a 0.1% otic solution for treating ear mites. It is not available in a more concentrated dosage form, so overdoses are relatively rare[1].

Toxicology

The therapeutic dosages of Milbemycin oxime (milbemycin) for heartworm prevention are 0.5 mg/kg in dogs and 2 mg/kg in cats. Mild clinical signs of ataxia, hypersalivation, mydriasis, and lethargy have been documented in ivermectin-sensitive dogs dosed at 5 to 10 mg/kg. In a separate report, two ABCB1-defective dogs developed mild signs (ataxia) after being dosed repeatedly with milbemycin for demodicosis; one dog received 0.8 mg/kg 2 days in a row, and the other dog received 1.5 mg/kg daily for 13 days before developing signs. Mild clinical signs have been reported to develop in normal dogs at 10 to 20 mg/kg and in cats and dogs with suspected ABCB1 gene deletions greater than 5 to 10 mg/kg. The most common clinical signs reported include ataxia, tremors, lethargy, vomiting, mydriasis, disorientation, and hypersalivation[1].

Veterinary Drugs and Treatments

Milbemycin tablets are labeled as a once-a-month heartworm preventative (Dirofilaria immitis) and for hookworm control (Ancylostoma caninum). It has activity against a variety of other parasites, including adult hookworms (A. caninum), adult roundworms (T. canis, T. leonina) and whipworms (Trichuris vulpis). In cats, milbemycin has been used successfully to prevent larval infection of Dirofilaria immitis.
Milbemycin, like ivermectin can be used for treatment of generalized demodicosis in dogs, but treatment can be significantly more expensive. It is likely safer to use in breeds susceptible to mdr1 genetic mutation (Collies, Shelties, Australian shepherds, etc.) at the doses used for this indication, but neuro toxicity is possible. Older dogs, those that have had a long duration of disease prior to treatment, and dogs with pododemodicosis appear have a lower success rate with milbemycin treatment.

References

[1] DVM, Valentina M. Merola, Paul A. Eubig DVM MS and MS. “Toxicology of Avermectins and Milbemycins (Macrocylic Lactones) and the Role of P-Glycoprotein in Dogs and Cats.” Veterinary Clinics of North America-Small Animal Practice 42 2 (2012): Pages 313-333.

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