The adenosine receptor activity of EMD 28422, a purine derivative with reported actions on benzodiazepine receptors.
The effects of a novel purine derivative, N6-[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). EMD 28422 was about 30 times less potent than CHA and 4 times less potent than NECA in displacing bound [3H]-L-PIA from specific binding sites in the rat brain, presumably reflecting adenosine A1-receptors. A similar relative potency was found using depression of field e.p.s.p. in the hippocampal slice in vitro. In isolated fat cells EMD 28422 was antilipolytic, but some 1000 times less potent than L-PIA. In rat isolated hippocampal slices, which have adenosine A2-receptors, EMD 28422 was more than 300 times less potent than NECA and in guinea-pig thymocytes, which similarly have A2-receptors, EMD 28422 was about 60 times less potent. The results are compatible with the opinion that EMD 28422 is a rather weak agonist at adenosine receptors, with limited selectivity for A1- or A2-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.
Dunwiddie
T V
TV
Fredholm
B B
BB
Jonzon
B
B
Sandberg
G
G
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001831:Body Temperature; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects*; D011983:Receptors, Purinergic; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D011983:Receptors, Purinergic; C025960:N(6)-(2-(4-chlorophenyl)bicyclo(2.2.2.)-octyl)(3)-adenosine; D000242:Cyclic AMP; D000241:Adenosine