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Zolantidine (SK&F 95282) is a potent selective brain‐penetrating histamine H 2 ‐receptor antagonist
Author(s) -
Calcutt C.R.,
Ganellin C.R.,
Griffiths R.,
Leigh B.K.,
Maguire J.P.,
Mitchell R.C.,
Mylek M.E.,
Parsons M.E.,
Smith I.R.,
Young R.C.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11406.x
Subject(s) - histamine , dimaprit , medicine , antagonist , histamine h2 receptor , endocrinology , receptor , histamine receptor , histamine h3 receptor , chemistry , cyclase , receptor antagonist , guinea pig , adenosine , pharmacology , biology
1 The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H 2 ‐receptors in guinea‐pig atrium and rat uterus. Only apparent pA 2 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 H 2 ‐receptors in guinea‐pig brain. The compound inhibited histamine stimulated adenylate cyclase (pK i 7.3) and dimaprit stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation (approx pA 2 7.63), and competed with [ 3 H]‐tiotidine binding (pK i 7.17). 3 Zolantidine is at least 30 fold more potent at H 2 ‐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 H 2 ‐receptor antagonist, and will be a valuable pharmacological tool for investigating possible physiological and pathological roles for histamine in the central nervous system.