Increased benzodiazepine receptor number elicited in vitro by a novel purine, EMD 28422

Skolnick, Phil; Lock, K.-L.; Paul, Steven M.; Marangos, Paul J.; Jones, Rochas; Irmscher, Klaus

doi:10.1016/0014-2999(80)90496-3

Cited by 25 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the compound had an extremely slow onset of action in the electrophysiological experiments and the effect once rison of the potency of EMD established was also difficult or impossible to wash )f other adenosine analogues in out. We have previously found that the time-course of ms action in this system is related to the time it takes for the compound to equilibrate with the slice and that this appears to be related to its lipophilicity (Dunwid-EMD NECA 2-CA L-PIA die (Skolnick et al, 1980a) and in vitro (Skolnick et al, 1980b;Fehske et >30 0.1 1.7 1.5 al., 1982). This effect has a dose-response relationship 20-30 1 -4 10 -25 100-1000 that is different from that found in the present study.…”

Section: Electrophysiological Experimentsmentioning

confidence: 98%

The adenosine receptor activity of EMD 28422, a purine derivative with reported actions on benzodiazepine receptors

Dunwiddie

Fredholm²,

Jonzon

et al. 1985

British J Pharmacology

View full text Add to dashboard Cite

show abstract

Section: Electrophysiological Experimentsmentioning

confidence: 98%

The adenosine receptor activity of EMD 28422, a purine derivative with reported actions on benzodiazepine receptors

Dunwiddie

Fredholm²,

Jonzon

et al. 1985

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…36 Recently a potent inhibitor of adenosine uptake, namely, dipyridamole, was shown to have relatively high affinity for benzodiazepine binding sites.37 Finally, certain N6substituted adenosine analogues, namely, JV6-[2-(4chlorophenyl)bicyclo[2.2.2]octyl]adenosine (EMD 28422), can increase the apparent levels of benzodiazepine receptors in brain membranes. 38 Clearly, the interrelationship of the sedative and muscle-relaxant actions of benzodiazepines and adenosine deserves further investigation. A naturally occuring adenosine analogue, namely, 1-methylisoguanosine, is a sedative and muscle relaxant, presumably through actions mediated by adenosine receptors, but it is also active as an antagonist of diazepam binding.…”

Section: Source and Disposition Of Adenosinementioning

confidence: 99%

Adenosine receptors: targets for future drugs

Daly¹

1982

J. Med. Chem.

698

369

View full text Add to dashboard Cite

“…It should be noted that barbiturates represent another class of compounds that enhance diazepam binding to the GABA-receptor-channel complex [39] and have similar potencies at such complexes and as antagonists at adenosine receptors [28,29], suggesting again structural analogies between certain regulatory sites on the GABA-receptor-channel complex and antagonist sites on adenosine receptors. A wide variety of purines and xanthines inhibit binding of diazepam to the GABA-receptor-channel complex [40] and one N 6 -substituted adenosine (EMD 28422) increases the apparent number of diazepam binding sites in brain membranes [41]. Further studies on other N 6 -substituted analogs of these anxiolytic pyrazolopyridines (Ia, Ib, Ic) will be necessary to define the structural parameters that contribute to potent antagonist activity at adenosine receptors.…”

Section: Pyrazolopyridinesmentioning

confidence: 99%

Non-xanthine heterocycles: Activity as antagonists of A1 and A2-adenosine receptors

Daly

Hong

Padgett

et al. 1988

Biochemical Pharmacology

View full text Add to dashboard Cite

A variety of non-xanthine heterocycles were found to be antagonists of binding of [ 3 H]phenylisopropyladenosine to rat brain A 1 -adenosine receptors and of activation of adenylate cyclase via interaction of N-ethylcarboxarnidoadenosine with A 2 -adenosine receptors in human platelet and rat pheochromocytoma cell membranes. The pyrazolopyridines tracazolate, cartazolate and etazolate were several fold more potent than theophylline at both A 1 -and A 2 -adenosine receptors. The pyrazolopyridines, however, were still many fold less potent than 8-phenyltheophylline and other 8-phenyl-1,3-dialkylxanthines. A structurally related N 6 -substituted 9-methyladenine was also a potent adenosine antagonist with selectivity for A 1 receptors. None of several aryl-substituted heterocycles, including a thiazolopyrimidine, imidazopyridines, benzimidazoles, a pyrazoloquinoline, a mesoionic xanthine analog and a triazolopyridazine exhibited the high potency typical of 8-phenyl-1,3-dialkylxanthines. A furyl-substituted triazoloquinazoline was very potent at both A 1 and A 2 receptors. A pteridin-2,4-dione, 1,3-dipropyllumazine, was somewhat less potent than theophylline at A 1 -and A 2 -adenosine receptors, whereas 1,3-dimethyllumazine was much less potent. A benzopteridin-2,4-dione, alloxazine, was somewhat more potent than theophylline. Other heterocycles with antagonist activity were the dibenzazepine carbamazepine and β-carboline-3-ethyl carboxylate. The phenylimidazoline clonidine had no activity, whereas a related dihydroxyphenylimidazoline was a weak noncompetitive adenosine antagonist.Xanthines, such as theophylline, caffeine and various 8-aryl-1,3-dialkylxanthines, have been widely used as antagonists of A 1 and A 2 -adenosine receptors [1]. The 8-aryl-1,3-dialkylxanthines are very potent at both subclasses of adenosine receptors [2][3][4][5][6][7][8][9][10][11]. Certain 8-aryl-1,3-dipropylxanthines exhibit selectivity for A 1 receptors [4,8,9] and certain caffeine analogs exhibit some selectivity for A 2 receptors [12,13]. Other classes of heterocyclic compounds exhibit antagonist activity at adenosine receptors. These include: 9-methyladenines [10,14], various pyrazolopyridines (etazolate, cartazolate, tracazolate) [15][16][17][18], various pyrazolopyrimidines [19,20], imidazopyrazines [21], a phenyl-substituted pyrazoloquinoline (CGS 8216) [22,23], a furyl-sub-stituted triazoloquinazoline (CGS 15943a) [24], a triazolopyridazine (CL218872) [15], various mesoionic analogs of xanthines [25], pteridin-2,4-diones (lumazine) and benzopteridin-2,4-diones [10,26], β-carbolines [15,27], barbiturates [28,29] and dibenzazepines (carbamazepine) [30][31][32][33]. A phenylaminoimidazoline, clonidine, has been reported to antagonize adenosine responses in physiological experiments [34].The non-xanthine adenosine antagonists have been largely neglected in behavioral and physiological studies, and little is known of structure-activity relationships within such METHODS MaterialsThe sources from which we obtained our mat...

show abstract

Increased benzodiazepine receptor number elicited in vitro by a novel purine, EMD 28422

Cited by 25 publications

References 23 publications

The adenosine receptor activity of EMD 28422, a purine derivative with reported actions on benzodiazepine receptors

The adenosine receptor activity of EMD 28422, a purine derivative with reported actions on benzodiazepine receptors

Adenosine receptors: targets for future drugs

Non-xanthine heterocycles: Activity as antagonists of A1 and A2-adenosine receptors

Contact Info

Product

Resources

About