%0 Journal Article %1 Lohse1988c %A Lohse, M. J. %A Klotz, K. N. %A Schwabe, U. %A Cristalli, G. %A Vittori, S. %A Grifantini, M. %D 1988 %J Naunyn Schmiedebergs Arch Pharmacol %K & Adenosine/*analogs Adenylate Adipose Animals Blood Brain/drug Corpus Cyclase/metabolism Humans Platelets/drug Purinergic/drug Rats Striatum/drug Tissue/drug derivatives/pharmacology effects/*metabolism effects/enzymology/metabolism effects/metabolism Receptor %N 6 %P 687-9 %T 2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3216901 %V 337 %X 2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for A1 adenosine receptors. Binding of 3HPIA to A1 receptors of rat brain membranes was inhibited by CCPA with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N6-cyclopentyladenosine (CPA). Binding of 3HNECA to A2 receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of CCPA. CCPA inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A1 receptor, with an IC50-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A1 adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA). CCPA represents the agonist with the highest selectivity for A1 receptors reported so far.

@article{Lohse1988c, abstract = {2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for A1 adenosine receptors. Binding of [3H]PIA to A1 receptors of rat brain membranes was inhibited by CCPA with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N6-cyclopentyladenosine (CPA). Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of CCPA. CCPA inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A1 receptor, with an IC50-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A1 adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA). CCPA represents the agonist with the highest selectivity for A1 receptors reported so far.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lohse, M. J. and Klotz, K. N. and Schwabe, U. and Cristalli, G. and Vittori, S. and Grifantini, M.}, biburl = {https://www.bibsonomy.org/bibtex/2271ef6afc3e0996b807f9ecea0a3dc10/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {834a5af86185b66e6c9c6ebe7214adfc}, intrahash = {271ef6afc3e0996b807f9ecea0a3dc10}, issn = {0028-1298 (Print) 0028-1298 (Linking)}, journal = {Naunyn Schmiedebergs Arch Pharmacol}, keywords = {& Adenosine/*analogs Adenylate Adipose Animals Blood Brain/drug Corpus Cyclase/metabolism Humans Platelets/drug Purinergic/drug Rats Striatum/drug Tissue/drug derivatives/pharmacology effects/*metabolism effects/enzymology/metabolism effects/metabolism Receptor}, month = Jun, note = {Lohse, M J Klotz, K N Schwabe, U Cristalli, G Vittori, S Grifantini, M In Vitro Research Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):687-9.}, number = 6, pages = {687-9}, shorttitle = {2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors}, timestamp = {2010-12-14T18:20:06.000+0100}, title = {2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3216901}, volume = 337, year = 1988 }