Specificity antagonists

Alkaloids are heterocyclic basic compounds and widespread in plants. Many of them have specific targets in organisms. For example, the alkaloids atropine and scopolamine of Belladonna are specific antagonists at muscarinic receptors. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

ATC A03FA06 A04AD Use anti-emetic, specific antagonist of peripheral and central dopamine receptors, reversible MAO-inhibitor... 

Cysteinyl leukotrienes can induce an early, transient fall in arterial pressure associated with sympathoadrenergic activation, plus a late rise in small coronary arteriolar resistance [32]. Using specific antagonists of CysFTi and CysFT2 [63] it will be possible to assess the each receptor s contribution to the cardiovascular effects of these vasoactive mediators. 

Thus the neurotransmitter role of ATP is well established in the periphary and also in sensory systems but its importance in the CNS remains to be elucidated (see Burnstock 1996). That requires the development of more specific antagonists and methods of mapping its location. The strong linkage of its P2x receptors to calcium currents may also provide a role for ATP in more long-term effects such as plasticity and neuronal development and death. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Matthys P, Hatse S, Vermeire K, et al. AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice. J Immunol 2001 167(8) 4686-4692. 

Fig. 4. Structure of UK-427,857 (maraviroc), a CCR5-specific antagonist from Pfizer currently in phase III studies for HIV treatment. The original hit from the high-throughput screening, compound UK107,543, is also shown.

Ginawi, O.T., Al-Majed, A.A., Al-Suwailem, A.K. NAN-190, a possible specific antagonist for meth-amphetamine. Regul. Toxicol. Pharmacol. 41 122, 2005. 

Lamant V, Mauco G, Braquet P, Chap H, Douste-Blazy L. (1987). Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Biochem Pharmacol. 36(17) 2749-52. 

Its effects should be selectively blocked by a specific antagonist and mimicked by a specific agonist. 

Ahlquist, in 1948, first proposed that noradrenaline could produce its diverse physiological effects by acting on different populations of adrenoceptors, which he termed a and ft receptors. This classification was based upon the relative selectivity of adrenaline for the a receptors and isoprenaline for the ft receptors drugs such as phentolamine were found to be specific antagonists of the a, and propranolol for the ft receptors. 

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