Xanthine derivatives as antagonists at A1 and A2 adenosine receptors
U. Schwabe, D. Ukena, and M. Lohse. Naunyn Schmiedebergs Arch Pharmacol, 330 (3):
212-21(September 1985)Schwabe, U Ukena, D Lohse, M J In Vitro Research Support, Non-U.S.
Gov't Germany, west Naunyn-Schmiedeberg's archives of pharmacology
Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21..
Abstract
A variety of alkylxanthines has been comparatively examined as antagonists
of A1 adenosine receptors in rat fat cells, rat and bovine cerebral
cortex and of A2 adenosine receptors in human platelets. With few
exceptions all xanthine derivatives with 7-position substituents
such as diprophylline, proxyfylline, pentoxifylline and etofylline
were less potent antagonists than xanthine itself which had Ki-values
of 170 mumol/l (A1) and 93 mumol/l (A2). Theophylline, caffeine and
3-isobutyl-1-methylxanthine were more potent than xanthine but nearly
equipotent antagonists at both receptor subtypes. 8-Phenyl substituents
considerably increased the antagonist potency at A1 and A2 receptors.
1,3-Diethyl-8-phenylxanthine was the most potent A2 antagonist (Ki
0.2 mumol/l) in human platelets. At A1 receptors 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine
(PACPX) was the most potent antagonist in all three tissues with
Ki-values from 0.3 to 8.6 nmol/l. Several 8-phenylxanthine derivatives
were remarkably selective antagonists at A1 receptors. 8-Phenyltheophylline
was approximately 700 times more potent as antagonist at A1 receptors
(bovine brain) than at A2 receptors (human platelets), and PACPX
was even 1,600 times more potent as A1 adenosine receptor antagonist.
These compounds offer a possibility for a subtype-selective blockade
of adenosine receptors.
Schwabe, U Ukena, D Lohse, M J In Vitro Research Support, Non-U.S.
Gov't Germany, west Naunyn-Schmiedeberg's archives of pharmacology
Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21.
%0 Journal Article
%1 Schwabe1985
%A Schwabe, U.
%A Ukena, D.
%A Lohse, M. J.
%D 1985
%J Naunyn Schmiedebergs Arch Pharmacol
%K & Adenosine Adenosine-5'-(N-ethylcarboxamide) Adenosine/analogs Adenylate Adipose Animals Blood Brain Cell Chemistry/drug Cyclase/metabolism Diphosphate/pharmacology Humans Male Membrane/enzymology/metabolism Platelets/metabolism Purinergic Rats Strains Surface/*drug Tissue/metabolism Xanthines/*pharmacology derivatives/pharmacology effects effects/metabolism Receptor Mice
%N 3
%P 212-21
%T Xanthine derivatives as antagonists at A1 and A2 adenosine receptors
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2997628
%V 330
%X A variety of alkylxanthines has been comparatively examined as antagonists
of A1 adenosine receptors in rat fat cells, rat and bovine cerebral
cortex and of A2 adenosine receptors in human platelets. With few
exceptions all xanthine derivatives with 7-position substituents
such as diprophylline, proxyfylline, pentoxifylline and etofylline
were less potent antagonists than xanthine itself which had Ki-values
of 170 mumol/l (A1) and 93 mumol/l (A2). Theophylline, caffeine and
3-isobutyl-1-methylxanthine were more potent than xanthine but nearly
equipotent antagonists at both receptor subtypes. 8-Phenyl substituents
considerably increased the antagonist potency at A1 and A2 receptors.
1,3-Diethyl-8-phenylxanthine was the most potent A2 antagonist (Ki
0.2 mumol/l) in human platelets. At A1 receptors 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine
(PACPX) was the most potent antagonist in all three tissues with
Ki-values from 0.3 to 8.6 nmol/l. Several 8-phenylxanthine derivatives
were remarkably selective antagonists at A1 receptors. 8-Phenyltheophylline
was approximately 700 times more potent as antagonist at A1 receptors
(bovine brain) than at A2 receptors (human platelets), and PACPX
was even 1,600 times more potent as A1 adenosine receptor antagonist.
These compounds offer a possibility for a subtype-selective blockade
of adenosine receptors.
@article{Schwabe1985,
abstract = {A variety of alkylxanthines has been comparatively examined as antagonists
of A1 adenosine receptors in rat fat cells, rat and bovine cerebral
cortex and of A2 adenosine receptors in human platelets. With few
exceptions all xanthine derivatives with 7-position substituents
such as diprophylline, proxyfylline, pentoxifylline and etofylline
were less potent antagonists than xanthine itself which had Ki-values
of 170 mumol/l (A1) and 93 mumol/l (A2). Theophylline, caffeine and
3-isobutyl-1-methylxanthine were more potent than xanthine but nearly
equipotent antagonists at both receptor subtypes. 8-Phenyl substituents
considerably increased the antagonist potency at A1 and A2 receptors.
1,3-Diethyl-8-phenylxanthine was the most potent A2 antagonist (Ki
0.2 mumol/l) in human platelets. At A1 receptors 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine
(PACPX) was the most potent antagonist in all three tissues with
Ki-values from 0.3 to 8.6 nmol/l. Several 8-phenylxanthine derivatives
were remarkably selective antagonists at A1 receptors. 8-Phenyltheophylline
was approximately 700 times more potent as antagonist at A1 receptors
(bovine brain) than at A2 receptors (human platelets), and PACPX
was even 1,600 times more potent as A1 adenosine receptor antagonist.
These compounds offer a possibility for a subtype-selective blockade
of adenosine receptors.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Schwabe, U. and Ukena, D. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/223ed2b8401c4469d5e6c0e9d448f3048/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {d54025acabbf006156f0ad9722420149},
intrahash = {23ed2b8401c4469d5e6c0e9d448f3048},
issn = {0028-1298 (Print) 0028-1298 (Linking)},
journal = {Naunyn Schmiedebergs Arch Pharmacol},
keywords = {& Adenosine Adenosine-5'-(N-ethylcarboxamide) Adenosine/analogs Adenylate Adipose Animals Blood Brain Cell Chemistry/drug Cyclase/metabolism Diphosphate/pharmacology Humans Male Membrane/enzymology/metabolism Platelets/metabolism Purinergic Rats Strains Surface/*drug Tissue/metabolism Xanthines/*pharmacology derivatives/pharmacology effects effects/metabolism Receptor Mice},
month = Sep,
note = {Schwabe, U Ukena, D Lohse, M J In Vitro Research Support, Non-U.S.
Gov't Germany, west Naunyn-Schmiedeberg's archives of pharmacology
Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21.},
number = 3,
pages = {212-21},
shorttitle = {Xanthine derivatives as antagonists at A1 and A2 adenosine receptors},
timestamp = {2010-12-14T18:22:57.000+0100},
title = {Xanthine derivatives as antagonists at A1 and A2 adenosine receptors},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2997628},
volume = 330,
year = 1985
}