Imiquimod

Absorption

Well absorbed through skin (as a cream)

Toxicity

Symptoms of overdose include flu-like symptoms, such as fever, fatigue, headache, nausea, diarrhoea and muscle pain.

Description

Aldara was launched in the US for the topical treatment of genital warts caused by human papillomavirus (HPV). It can be prepared in a six step approach beginning with the nucleophilic substitution of 4-chloro-3-nitroquinolone with isobutylamine or via a thermal electrocyclic ring closure of 1 - and 2-azahexatriene systems. Aldara has antiviral and antitumor properties, with the former activity arising from the induction of cytokines, in particular, INF-α. Aldara also induces TNF-γ, IL-1α, IL-1β, IL-1ra, IL-6, IL-8, IL-10, GM-CSF, G-CSF and MID-la formation 1-4 hr after stimuli. The exact cells responsible for the response have not been determined, however, it is not activating T lymphocytes, NK cells, B lymphocytes, or dendritic stem cells but monocytes (CD14⁺, CD36⁺, HLA-DR⁺, HLA-DQ^±, CD19^-, CD16^- and CD23^-) are partly responsible. The speculation is that Aldara may interact with a kinase modulating the transduction pathway leading to cytokine genes. There is no direct antiviral activity (induction of IFN does not follow true dose response) and it is not mutagenic. The hydroxylated metabolite also induces IFN-α.

Chemical properties

White to off white crystalline powder

Originator

3M Pharmaceuticals (US)

The Uses of Imiquimod

Imiquimod is a caspase 3 activator which acts as an immunomodulator and displays antiviral and anti-tumor activity. It is a patient-applied cream used for the treatment of genital warts and basal cell carcinoma. It is also used to cure actinic keratosis on the face and scalp. It belongs to a group of drugs called immune response modifiers, which work by activating the immune system to fight abnormal skin growth.

The Uses of Imiquimod

An immune response modifier. It stimulates the production of interferon-a

The Uses of Imiquimod

raw material for Latamoxef, Cefminox, Ceftizoxime, Cefoxitin, Cefmetazole

Indications

For the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults. Also indicated for the treatment of external genital and perianal warts/condyloma acuminata in individuals 12 years old and above.

Background

Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. Miquimod is also used to treat a skin condition of the face and scalp called actinic keratoses and certain types of skin cancer called superficial basal cell carcinoma.

What are the applications of Application

Imiquimod is a TLR7 activator and angiogenesis inhibitor

Indications

Imiquimod (Aldara) is a topical immune response modifier approved for the treatment of anogenital warts (condylomata acuminata). The exact mechanism of action is unknown; it has no direct antiviral activity in vitro. It is thought to work in vivo by inducing the production of tumor necrosis factor (TNF α ), interferons (IFN)α and γ , and other cytokines with antiviral activity. It may also be useful for treatment of other types of warts, molluscum contagiosum, and certain forms of skin cancer. Local irritant reactions related to the frequency of application are common.

Definition

ChEBI: Imiquimod is an imidazoquinoline fused [4,5-c] carrying isobutyl and amino substituents at N-1 and C-4 respectively. A prescription medication, it acts as an immune response modifier and is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. It has a role as an antineoplastic agent and an interferon inducer.

brand name

Aldara (3M Pharmaceuticals).

Pharmaceutical Applications

An imidazoquinoline used for the treatment of genital and perianal warts. While the mechanism of action is not precisely known, it is thought to induce interferon. It has no direct antiviral activity. The 5% cream applied three times a week for up to 16 weeks resulted in total wart clearance in 50% of patients, with a better response in women than in men. Local reactions are common and include erythema, erosion, excoriation and edema.

Biological Activity

Immunomodulator that displays antiviral and antitumor activity. Acts as a Toll-like receptor 7 (TLR-7) agonist; stimulates proinflammatory cytokine production and activates NF- κ B.

Biochem/physiol Actions

Imiquimod is a caspase 3 activator, which directly induces procaspase 3 cleavage to active caspase 3. Imiquimod induces apoptosis in vivo in basal cell carcinoma. Its anti-tumor activity is related to the induction of apoptosis. Imiquimod has anti-angiogenic, anti-inflammatory, anti-viral activities. Imiquimod also acts as an immune response modulator inducing the secretion of various cytokines and chemokines.

Mechanism of action

Imiquimod (Aldara) is an imidazoquinolone amine that is an immune responsemodifier. Its exact mechanism is unknown in the topical treatment of HPV and molluscum contagiosum but may be related to the immunomodulating effect of the drug. It is also effective in the treatment of actinic keratoses and superficial basal cell carcinoma.
It induces production of a variety of cytokines and can enhance cell-mediated cytolytic antiviral activity. It is a rapid and potent inducer of interferon-α, interleukin?1 α and β, interleukin 6, interleukin 8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and granulocyte colonystimulating factor. Systemic absorption is minimal. It is generally well tolerated. Adverse local reactions include erythema, erosion, excoriation, flaking, and edema of the treatment sites.

Pharmacokinetics

Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratoses. Imiquimod can also be used to treat certain types of skin cancer called superficial basal cell carcinoma. Imiquimod is particularly useful on areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs.

Veterinary Drugs and Treatments

An immune response modifier, imiquimod may be useful in the treatment of a variety of topical conditions in animals. It is labeled for use on humans as a treatment for genital or perianal warts, superficial basal cell carcinomas and actinic keratoses of the face and scalp. In dogs and cats, imiquimod potentially may be of benefit in treating feline herpes virus dermatitis, actinic keratosis, squamous cell carcinoma and Bowen’s disease, papillomas virus lesions, and localized solar dermatitis or solar carcinoma in situ. In horses, imiquimod has been anecdotally used with success in treating sarcoids.
Imiquimod stimulates the patient’s own immune system to release a variety of cytokines including interferon-alpha and interleukin- 12. Imiquimod itself does not have in vitro activity against wart viruses, but stimulates monocytes and macrophages to release cytokines that induce a regression in viral protein production.

Metabolism

Not Available

storage

+4°C

References

1) Hemmi?et al.?(2002),?Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway;?Nat. Immunol.?3?196 2) Stanley?et al.?(2002),?Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential;?Clin. Exp. Dermatol.?27?571 3) Schoen?et al.?(2006),?The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion;?J.Invest.Dermatol.?126?1338 4) Kan?et al.?(2012),?Imiquimod Suppresses Propagation of Herpes Simplex Virus 1 by Upregulation of Cystatin A via the Adenosine Receptor A1?Pathway.; J. Virol.?86?10338 5) Urosevic?et al.?(2004),?Imiquimod Treatment Induces Expression of Opioid Growth Factor Receptor; Clin. Cancer Res.?10?4959 6) Zagon?et al.?(2008),?Imiquimod Upregulates the Opioid Growth Factor Receptor to Inhibit Cell Proliferation Independent of Immune Function.; Exp. Biol. Med.(Maywood)?233?968