Imiquimod

drugbox
IUPAC_name = 1-isobutyl-1"H"-imidazo [4,5-"c"] quinolin-4-amine

---

width = 180px
CAS_number = 99011-02-6
ATC_prefix = D06
ATC_suffix = BB10
PubChem = 57469
DrugBank = APRD01030
C = 14 |H = 16 |N = 4
molecular_weight = 240.304 g/mol
smiles = CC(C)Cn1cnc2c(N)nc3ccccc3c12
bioavailability =
protein_bound =
metabolism =
elimination_half-life = 30 hours (topical dose), 2 hours (subcutaneous dose)
licence_EU = Aldara
licence_US = Imiquimod
pregnancy_AU = B1
pregnancy_US = C
pregnancy_category=
legal_AU =
legal_CA =
legal_UK = POM
legal_US = Rx-only
legal_status =
routes_of_administration = Topical

Imiquimod (INN) is a prescription medication that acts as an immune response modifier. It is marketed by MEDA AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade name Aldara and by Mochida as Beselna.

Uses

Imiquimod is a patient-applied cream used to treat certain diseases of the skin, including skin cancers (basal cell carcinoma, Bowen's disease [cite journal |author=van Egmond S, Hoedemaker C, Sinclair R |title=Successful treatment of perianal Bowen's disease with imiquimod |journal=Int J Dermatol |volume=46 |issue=3 |pages=318–9 |year=2007 |pmid=17343595 |doi=10.1111/j.1365-4632.2007.03200.x] , superficial squamous cell carcinoma, some superficial malignant melanomas, and actinic keratosis) as well as genital warts (Condylomata acuminata). It has also been tested for treatment of Molluscum contagiosum, VIN (Vulvar intraepithelial neoplasia)cite web |url=http://content.nejm.org/cgi/content/short/358/14/1465 |title=Treatment of Vulvar Intraepithelial Neoplasia with Topical Imiquimod |author=Manon van Seters, M.D., Marc van Beurden, M.D., Ph.D., Fiebo J.W. ten Kate, M.D., Ph.D., Ilse Beckmann, M.Sc., Ph.D., Patricia C. Ewing, M.D., Marinus J.C. Eijkemans, Ph.D., Marjolein J. Kagie, M.D., Ph.D., Chris J.M. Meijer, M.D., Ph.D., Neil K. Aaronson, Ph.D., Alex KleinJan, Ph.D., Claudia Heijmans-Antonissen, B.Sc., Freek J. Zijlstra, Ph.D., Matthé P.M. Burger, M.D., Ph.D., and Theo J.M. Helmerhorst, M.D., Ph.D|accessdate=2008-04-30] and VAIN (vaginal intraepithelial neoplasia). [cite journal |author=Buck HW, Guth KJ |title=Treatment of vaginal intraepithelial neoplasia (primarily low grade) with imiquimod 5% cream |journal=J Low Genit Tract Dis |pmid=17051086]

History

The original FDA approval was on February 27, 1997, FDA Application No. (NDA) 020723, by Graceway.

Since then, the label has been revised many times. Adverse side effects have been reported, in some cases serious and systemic.

Mechanism of action

The exact mechanism of action in which imiquimod and its analogs activate the immune system is not yet known. Nevertheless, it is known that imiquimod activates immune cells by ligating the toll-like receptor 7 (TLR7), commonly involved in pathogen recognition, on the cell surface.Hemmi, H., "et al." Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. "Nat Immunol.". 2002 "3"(2):196-200. PMID 11812998.] Cells activated by imiquimod via TLR-7 secrete cytokines (primarily interferon-α (IFN-α), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)). Sauder, D.N., Imiquimod: modes of action. "British Journal of Dermatology". 2003 149(Suppl. 66):5-8. PMID 14616337] There is evidence that imiquimod, when applied to skin, can lead to the activation of Langerhans cells, which subsequently migrates to local lymph nodes to activate the adaptive immune system.Miller, R.L., "et al." Imiquimod applied topically: a novel immune response modifier and a new class of drug. "Int J Immunopharmacol". 1999 Jan;21(1):1-14. PMID 10411278] Other cell types activated by imiquimod include natural killer cells, macrophages and B-lymphocytes.

New research has shown that imiquimod's anti-proliferative effect is totally independent of immune system activation or function. Imiquimod exerts its effect by increasing levels of the opioid growth factor receptor (OGFr). Blocking OGFr function with siRNA technology resulted in loss of any antiproliferative effect of imiquimod. [cite journal |author=Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ |title=Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function |journal=Exp. Biol. Med. (Maywood) |volume=233 |issue=8 |pages=968–79 |year=2008 |month=August |pmid=18480416 |doi=10.3181/0802-RM-58 |url=]

References

External links

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* [http://www.npsradar.org.au/site.php?page=1&content=/npsradar/content/imiquimod.html NPS RADAR]
* [http://www.aldara.com Aldara.com]