Proprietà farmacologiche e possibilità terapeutiche dei farmaci che agiscono su recettori degli endocannabinoidi

Recenti ricerche hanno indicato che i composti che agiscono direttamente sui cannabinoidi (CB) e recettori possono avere un potenziale terapeutico.
Due settori sono focalizzati: a) l’eventuale uso di agonisti dei recettori CB e CB2-agonisti selettivi per il trattamento del dolore, e b) la possibile utilità di agonisti del recettore CB2 per la prevenzione di riacutizzazioni stress-indotte di affezioni cutaneee, come la psoriasi. Una seconda area di sviluppo del farmaco al momento è quella di antagonisti dei recettori CB1 / agonisti inversi.

Curr Drug Targets CNS Neurol Disord. 2005 Dec;4(6):685-96.
Pharmacological properties and therapeutic possibilities for drugs acting upon endocannabinoid receptors.
Fowler CJ.

Clinical trial data are beginning to emerge with respect to the therapeutic efficacy of cannabis extracts for the treatment of chronic pain. Although there is some evidence of efficacy, a major issue concerns the narrow margin between doses producing therapeutic effects and those producing the “highs” associated with cannabis misuse. In addition, long-term use is associated with an increased risk of psychiatric illness. These negative aspects constrain the doses of cannabis extracts and psychoactive cannabinoids that can be given to patients, and raise the risk that properly conducted clinical trials with too low dosages will impact negatively on subsequent drug development in this field. However, recent research has opened up a number of avenues whereby compounds acting directly upon cannabinoid (CB) receptors may have therapeutic potential. In this review, two such areas are discussed, namely a) the possible use of peripherally acting CB agonists and CB2 receptor-selective agonists for the treatment of pain, and b) the possible utility of CB2 receptor agonists for the prevention of stress-induced exacerbations of skin disorders such as psoriasis. A second area of drug development at present is that of CB1 receptor antagonists/inverse agonists, spearheaded by rimonabant, for the treatment of obesity and as an aid for smoking cessation. An important aspect of these compounds is their efficacy and selectivity, and this is discussed in detail in the present review.

 malattie infiammatorie della pelle

L’epidermide, epitelio squamoso autorinnovantesi composto di vari strati di cheratinociti, è importante barriera di difesa.
Proteasi endogene ed esogene, quali kallikreina, matriptasi, caspasi, catepsine, e proteasi derivate da microrganismi sono in grado di attivare e disattivare le molecole di difesa dell’epidermide umana.
Inibitori delle proteasi, come likeLEKTI, elafin, SLPI, SERPIN, e cystatin regolano le attività proteolitiche e contribuiscono alla integrità e funzione di barriera protettiva della pelle.
Variazioni dell’equilibrio proteolitico della pelle possono provocare infiammazione, eritema, desquamazione e prurito.
Sono riassunte le attuali conoscenze sul come proteasi, loro inibitori e loro proteine bersaglio, tra cui filaggrina, recettori proteasi-attivati e corneodesmosina, contribuiscono alla patofisiologia della infiammazione e sottolineano il loro ruolo in comuni malattie infiammatorie della pelle, come dermatite atopica, rosacea, e psoriasi.

Cutis. 2009 Oct; 84 (4) :207-14.
Reddish, scaly, and itchy: how proteases and their inhibitors contribute to inflammatory skin diseases.
Meyer-Hoffert U.


The skin protects us from water loss and mechanical damage. The surface-exposed epidermis, a self-renewing stratified squamous epithelium composed of several layers of keratinocytes, is most important in the barrier defense against these challenges.
Endogenous and exogenous proteases such as kallikreins, matriptase, caspases, cathepsins, and proteases derived from microorganisms are important in the desquamation process of the stratum corneum and are able to activate and inactivate defense molecules in human epidermis.
Protease inhibitors such as like LEKTI, elafin, SLPI, SERPINs, and cystatins regulate their proteolytic activity and contribute to the integrity and protective barrier function of the skin.
Changes in the proteolytic balance of the skin can result in inflammation, which leads to the typical clinical signs of redness, scaling, and itching.
This review summarizes the current knowledge of how proteases, their inhibitors, and their target proteins, including filaggrin, protease-activated receptors, and corneodesmosin, contribute to the pathophysiology of inflammation of the skin and highlight their role in common inflammatory skin diseases such as atopic dermatitis, rosacea, and psoriasis.