Impromidine is a partial histamine H₂‐receptor agonist on human ventricular myocardium

Abstract

1 The inotropic effects of impromidine have been studied and compared with those of histamine on human isolated left ventricular preparations stimulated at I Hz. Both drugs caused concentrationrelated increases in force of contraction and were of similar potency, although the maximum response to impromidine was markedly and significantly less than that to histamine. 2 The positive inotropic responses of impromidine were inhibited by cimetidine 1 x 10-5M, consistent with histamine H2-receptor involvement. 3 Impromidine 1 x 10-4 M inhibited maximal responses to histamine to a level equal to the maximal impromidine response; however, impromidine did not inhibit responses to isoprenaline. 4 Positive inotropic activity and inhibition ofmaximal responses to histamine occurred over a similar impromidine concentration-range. 5 Impromidine displaced histamine concentration-response curves to the right, whereas mepyramine had no effect on responses to histamine. 6 It is concluded that impromidine has positive inotropic activity on the human ventricle, that the response is mediated via histamine H2-receptors, and that impromidine is a partial agonist compared with histamine.

Effects of histamine H2 receptor agonists and antagonists on the isolated guinea pig gallbladder

“…As expected, impromidine was the most potent H, receptor agonist; however, in contrast with results obtained in other H, receptor assays, i.e. guinea pig papillary muscle, human myocardium and rat isolated stomach, where efficacy values ranged from 40 to 80% [2,13,16,261…”

A three‐parameter two‐state model of receptor function that incorporates affinity, efficacy, and signal amplification

“…The case of impromidine and histamine, a frequently used example (English et al. ), is used here to illustrate fitting (Fig. ).…”

“…For example, the case of impromidine and histamine (English et al. ) is a frequently used example (Fig. ), and there are many others in more recent literature (Hoyer and Boddeke ; Tadori et al.…”

Structure-Activity Relationships of Histamine H2 Receptor Ligands+

“…Burimamide (40) was the first histamine receptor antagonist that showed selectivity for H 2 R vs. H 1 R [7]. It exhibits rather low affinity for the H 2 R and, since the discovery of the H 3 R, it is known that burimamide is considerably more potent at the H 3 R than at the H 2 R (pA 2 : 7.2 (H 3 R) vs. 5.1 (H 2 R) [1]).…”

“…2), the prototypical guanidine-type H 2 R agonist, is ~50-fold more potent than histamine in increasing heart rate in the isolated guinea pig right atrium, a standard model used for the pharmacological characterisation of H 2 R ligands. It is a full agonist in the atrium but, depending on the species and the tissue studied, its intrinsic activity may be lower [1,[37][38][39][40][41][42][43]. Numerous impromidine analogues have been synthesised and analysed for agonistic activity at the H 2 R (for a review see [15]).…”