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The adenosine receptor activity of EMD 28422, a purine derivative with reported actions on benzodiazepine receptors
Author(s) -
Dunwiddie T.V.,
Fredholm B.B.,
Jonzon B.,
Sandberg G.
Publication year - 1985
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.1476-5381.1985.tb16142.x
Subject(s) - receptor , adenosine receptor , purine , adenosine , benzodiazepine , pharmacology , adenosine a1 receptor , chemistry , derivative (finance) , gabaa receptor , neuroscience , biochemistry , biology , agonist , financial economics , economics , enzyme
1 The effects of a novel purine derivative, N 6 ‐[2‐(4‐chlorophenyl)‐bicyclo‐2.2.2.octyl‐(3)]‐adenosine (EMD 28422), that has been found to influence central benzodiazepine receptors, has been compared to those of other adenosine analogues such as l ‐phenylisopropyladenosine ( l ‐PIA), cyclohexyladenosine (CHA) and adenosine‐5′‐N‐ethyl‐carboxamide (NECA). 2 EMD 28422 was about 30 times less potent than CHA and 4 times less potent than NECA in displacing bound [ 3 H]‐ l ‐PIA from specific binding sites in the rat brain, presumably reflecting adenosine A 1 receptors. A similar relative potency was found using depression of field e.p.s.p. in the hippocampal slice in vitro . 3 In isolated fat cells EMD 28422 was antilipolytic, but some 1000 times less potent than l ‐PIA. 4 In rat isolated hippocampal slices, which have adenosine A 2 ‐receptors, EMD 28422 was more than 300 times less potent than NECA and in guinea‐pig thymocytes, which similarly have A 2 ‐receptors, EMD 28422 was about 60 times less potent. 5 The results are compatible with the opinion that EMD 28422 is a rather weak agonist at adenosine receptors, with limited selectivity for A 1 ‐ or A 2 ‐receptors. The compound is highly lipophilic, which plays a role in determining its potency in a given biological system. The results are discussed in relation to reported adenosine modulation of benzodiazepine receptors.