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Histamine release has been detected biologically after exposure of human right atrial biopsy samples to compound 48/80. Human right atrial samples contain large quantities of histamine, 1035 +/- 65 ng/g fresh weight. Exposure of untreated electrically paced atrial strips to compound 84/80, 300 micro/ml, caused an increase in the force of atrial contraction similar to that caused by histamine. Pretreatment of strips with cimetidine, 3.16 x 10(-5) M, prevented the inotropic response to compound 48/80. It is concluded that mast cell degranulation in human atrial tissue can cause sufficient release of histamine to modify the function of the heart.

1. The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H2-receptors in guinea-pig atrium and rat uterus. Only apparent pA2 values of 7.46 and 7.26 respectively could be calculated since the slopes of the Schild plots were significantly less than unity. 2. Zolantidine is equally potent as an antagonist at histamine H2-receptors in guinea-pig brain. The compound inhibited histamine stimulated adenylate cyclase (pKi 7.3) and dimaprit stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation (approx pA2 7.63), and competed with [3H]-tiotidine binding (pKi 7.17). 3. Zolantidine is at least 30 fold more potent at H2-receptors than at other peripheral and central receptors investigated. 4. Infusion of zolantidine into rats produces a brain concentration greater than the plateau blood concentration (brain/blood ratio 1.45). 5. Zolantidine is thus characterized as a potent selective brain-penetrating H2-receptor antagonist, and will be a valuable pharmacological tool for investigating possible physiological and pathological roles for histamine in the central nervous system.