The effects of cimetidine on histamine atrial chronotropic receptor activity

Clinically useful histamine antagonists have been reported to be specific for H1- or H2-receptors. However, data is accumulating that the specificity of those agents may be relative. This study was undertaken in an attempt to clarify this point. Histamine stimulates the chronotropic responses of rabbit atria by acting on both H1- and H2-receptors. Cimetidine (H2-antagonist) and diphenhydramine (H1-antagonist) both cause some inhibition of the histamine response, but there is no evidence of competitive blockade with these antagonists given separately or in combination. 4-Methylhistamine (H2-agonist) stimulates chronotropic activity, and both H1- and H2-antagonists reduce this response to some degree. 2-Methylhistamine (H1-agonist) is a less effective agonist (perhaps rabbit atria contain fewer H1-receptors), but the response is also decreased by either H1-or H2-antagonists. These two "specific" agonists were combined to stimulate the histamine responses, and the antagonists were given simultaneously. The results were qualitatively similar to those obtained with histamine. The question remains: (1) are these agonists and antagonists specific or (2) are the rabbit atrial chronotropic receptors not typical of the H1- and H2-type receptor?