Agonist disease

The sales of antagonists of receptors, eg, diphenhydramine, terfenadine, and astemizole, used in the treatment of allergic diseases, represent 1% of the overall pharmaceutical market, ie, 1.7 biUion (U.S.). antagonists, eg, cimetidine and ranitidine, are effective in peptic ulcer disease and esophageal reflux. Sales represent 3.5% of the world market, ie, 6 biUion (U.S.). agonists or antagonists have not yet found a clear indication. 

Presently, only adenosine itself is approved for clinical use. It is used widely in the treatment of supraventricular tachycardia and in cardiac stress imaging to assess coronary artery disease [5]. Other agonists and antagonists and an allosteric modulator of the Ai receptor are in clinical trials for a variety of indications. 

Selective AR agonists are undergoing clinical trials for cardiac arrhythmias and pain (Ai) cardiac imaging and inflammation (A2a) colon cancer, rheumatoid arthritis, psoriasis, and dry eye (A3). Selective AR antagonists are either in or advancing toward clinical trials for kidney disorders (Ax) Parkinson s disease (A2a) diabetes and asthma (A2B) cancer and glaucoma (A3). 

Synthetic steroid with strong glucocorticoid-agonistic activity. Dexamethasone is over 10 times more potent than cortisol due to a higher binding affinity for glucocorticoid receptor and a decreased clearance rate of the compound. Due to its potency, dexamethasone is widely used in the clinics for the treatment of inflammatory diseases. 

Amyotropic lateral sclerosis (ALS) 3. AEA and 2-AG increase in the spinal cord of SOD1 transgenic mice, a model of ALS, to inhibit disease progress 3. CB2 receptor agonists or inhibitors of degradation... 

Target validation, to determine that a gene product is causative of disease symptoms or that activation of the target protein ameliorates disease symptoms. Agonist/activator or an inhibitor which may be therapeutic could be identified using microarrays... 

Johnson M (2004) Interactions between corticosteroids and beta2-agonists in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 1 200-6... 

The PAR family represents a novel target for drug therapy. Therapeutic approaches with most clinical benefit may rely upon the development of both agonists and antagonists, either of which could be utilised dqiending upon the disease condition [3]. 

From these studies it is clear that the progression of PAR-based therapy relies upon the future development of new specific agonists and antagonists for PARs 2-4 with much higher potencies than those currently available, with an efficient mode of delivery to target sites. However despite these problems the PARs still rqiresent one of the most attractive therapeutic targets for a number of disease states. 

PI (adenosine) receptors were explored as therapeutic targets before P2 receptors. Adenosine was identified early and is in current use to treat supraventricular tachycardia. A2a receptor antagonists are being investigated for the treatment of Parkinson s disease and patents have been lodged for the application of PI receptor subtype agonists and antagonists for myocardial ischaemia and reperfusion injury, cerebral ischaemia, stroke, intermittent claudication and renal insufficiency. 

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