Histamine-related agonists

Comparison of the Antagonism by Burimamide of the Actions of Histamine and Two Related Agonists on Guinea-Pig Atria... 

Franke, R. and Buschauer, A. (1992) Quantitative structure-activity relationships in histamine H2-agonists related to impromidine and arpromidine. Eur. J. Med. Chem., 27, 443-448. 

Phentolamine is a potent competitive antagonist at both K and k2 receptors (Table 10-1). Phentolamine reduces peripheral resistance through blockade of K receptors and possibly k2 receptors on vascular smooth muscle. Its cardiac stimulation is due to antagonism of presynaptic k2 receptors (leading to enhanced release of norepinephrine from sympathetic nerves) and sympathetic activation from baroreflex mechanisms. Phentolamine also has minor inhibitory effects at serotonin receptors and agonist effects at muscarinic and Hi and H2 histamine receptors. Phentolamine s principal adverse effects are related to cardiac stimulation, which may cause severe tachycardia, arrhythmias, and myocardial ischemia. Phentolamine has been used in the treatment of pheochromocytoma. Unfortunately oral and intravenous formulations of phentolamine are no longer consistently available in the United States. 

Palitzsch, K.D., Horales, R.E., Kronauge, J.F., Szabo, S., 1989. Biphasic effect of histamine on hemorrhagic mucosal lesions is related to vascular permeability studies with histamine, Hi-, H2- and H3-agonists and bradykinin. Gastroenterology 96, (Suppl.) A381. 

Due to its high selectivity and potency at H3 receptors (/ )-a-methylhistamine (12) is nowadays used as the standard agonist in pharmacological assays related to this receptor. With regard to its pharmacodynamic properties, which were substantiated in preclinical studies [40], (R)-a-methylhistamine (12) meets all criteria of a potential drug substance. However, in contrast to its pharmacodynamic potential (ft)-a-methyl-histamine (12) suffers from its pharmacokinetic drawbacks which limit its use in both pharmacological and conceivable clinical studies. 

Histamine receptors are related to skin barrier function.44 Three different types of histamine receptors, HI, H2, and H3 have been reported. First, topical application of histamine HI and H2 receptor antagonists accelerated the barrier repair. Histamine itself, H2 receptor agonist, and histamine releaser delayed the barrier repair. Histamine H3 receptor antagonist and agonist did not affect the barrier recovery rate. Topical application of the HI and H2 receptor antagonists prevented the epidermal hyperplasia induced by barrier disruption under low humidity. The mechanism of the relationship between the histamine receptors and the barrier repair process has not been elucidated yet. 

The identification of selectively acting agonists, chemically related to histamine, provides a valuable basis for studying the medicinal chemistry of histamine. Thus, 2-pyridylethylamine (, R=H) and 2-thia-zolylethylamine (4) have appreciable activity as agonists at Hj receptors and therefore indTcate that although the N -H tautomer (1) of histamine is... 

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