H -blockers

R. Frank, W. Heikens, G. Heisterberg-Moutsis, H. Blocker, Nucl. Acids Res. 1983,... 

Barth H, Blocker D, Aktories K. The uptake machinery of clostridial actin ADP-ribosylating toxins—a cell delivery system for fusion proteins and polypeptide drugs. Naunyn Schmiedebergs Arch Pharmacol 2002 366(6) 501-512. 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

Classically, these receptors have also been divided into three groups. The first of these, the Hj receptors, were described by Schild in 1966. The Hj receptors were discovered in 1972 by Black et al. The Hj receptor subtype was described by Arrang in 1983. The Hj receptor is found in the smooth muscle of the intestines, bronchi, and blood vessels and is blocked by the classical antihistamines. The Hj receptor, present in gastric parietal cells, in guinea pig atria, and in the uterus, does not react to H, blockers but only to specific Hj antagonists. Hj receptors also appear to be involved in the immunoregulatory system and may be present in T lymphocytes, basophil cells, and mast cells. Hj receptors are found predominantly in brain but are also localized in stomach, lung, and cardiac tissue. 

Orth, J.H., Blocker, D., and Aktories, K. 2003. Hisl205 and Hisl223 are essential for the activity of the mitogenic Pasteurella midtocida toxin. Biochemistry 42(17) 4971 -977. 

Histamine H, Blockers From Relative Failures to Blockbusters Within Series of Analogues 401... 

Design, International Workshop 1988 (ed. H. Blocker, J. CoUtns, R. D. Schmid and D. Schomburg), Chemie Wemherm, Basel, 1989, pp. 139-44... 

L. Grotjahn, R. Frank, and H. Blocker, Proc. 31st Annu. Conf. Mass Spectrom. Allied Top. 

R190 U. Schmitz, F. J. H. Blocker and T. L. James, Standard DNA Duplexes and RNAiDNA Hybrids in Solution , p. 253... 

The use of H - blockers in the treatment of hypertension has long been in disrepute However, the discovery of the unique a-blocking actions of prazosin has generated renewed Interest in this form of treatment. The pharmacological and clinical effects of this drug have been reviewed. ... 

Histamine is in mast cells, basophils, and platelets. Human skin mast cells express H H2, and H4 receptors, but not H3 receptors. Hi and H2 receptors are involved in wheal formation and erythema, whereas only Hi-receptor agonists cause pruritus. Complete blockade of Hi-receptors does not totally relieve itching, and combinations of Hi and H2 blockers may be superior to H, blockers alone. 

Ingestion of an antacid (alternatively an H, blocker or proton pump inhibitor) results in an increase in the pH of the gastric milieu. Because the pKz of aspirin (a weak acid) is 3.5, and therefore exists mainly in nonionized form in the gastric milieu, an increase in gastric pH would shift the equilibrium to the right, resulting in an increase in the ionized form and decreased absorption of the drag. 

Which ethylenediamine-type H, blocker is used in combination with pentazocine for drug abuse treatment ... 

Gut Atropine, methscopolamine, and propantheline were used in acid-peptic disease to reduce acid secretion, but they are not as effective as H,-blockers such as cimetidine, and they cause far more frequent and severe adverse effects. Pirenzepine is an M -selective muscarinic blocker (available in Europe but not tbe USA) that may be more useful in peptic ulcer. Muscarinic blockers can also be used to reduce cramping and hypermotility in transient diarrheas, but opioids such as diphenoxylate (Chapter 31) are more effective. 

B. Mechanism and Effects H, blockers are competitive pharmacologic antagonists at the H, receptor these drugs have no effect on histamine release from storage sites. They are more effective if given before histamine release occurs. 

A. Oassification and Prototypes Four H, blockers are available cimetidine is the prototype. Ranitidine, famotidine, and nizatidine differ only in being slightly less toxic than cimetidine. These drugs do not resemble H, blockers structurally. They are orally active, with half-lives of 1-3 hours. Because they are relatively nontoxic, they can be given in large doses, so that the duration of action of a single dose may be 12-24 hours. 

D. Toxicity Cimetidine is a potent inhibitor of hepatic drug-metabolizing enzymes and may also reduce hepatic blood flow. Cimetidine also has significant antiandrogen effects in patients receiving high doses. Ranitidine has a weaker inhibitory effect on hepatic drug metabolism neither it nor the other H, blockers appear to have endocrine effects. 

---