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Chemical Compound Review:

CCPA (2R,3R,4S,5R)-2-[2-chloro-6...

Synonyms: CHEMBL284969, C7938_SIGMA, CHEBI:152938, AC1L3XBY, KB-23064, ...

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Disease relevance of BRN 4888162

Conscious rabbits were pretreated with intravenous boluses of saline or the A1 receptor-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), and infarct size in response to 30-minute ischemia/120-minute reperfusion was assessed 24 hours later [1].
After acute administration in conscious rats, the A1 agonist 2-chloro-N6-cyclopentyladenosine induced dose-related hypotension (eg, 0.03 mg/kg; peak, -70 mm Hg; time to peak, 0.34 hour) and bradycardia (eg, 0.03 mg/kg; peak, -186 beats per minute [bpm]; time to peak, 0.38 hour) [2].
Myocardial infarct size was measured in open-chest anesthetized rats 24 h after treatment with vehicle or the adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 100 microg/kg ip) [3].
Recent studies have demonstrated that the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and the adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) produce a delayed phase of protection against infarction similar to the late phase of ischemic preconditioning (PC) [4].
Adenosine A1-receptor activation with 2-chloro-N6-cyclopentyladenosine (CCPA) decreased NE release by approximately 50% in hearts from both untreated and pertussis toxin-pretreated rats [5].

Psychiatry related information on BRN 4888162

Furthermore, local release of adenosine did not affect locomotor activity, whereas systemic application of the A1 agonist 2-chloro-N6-cyclopentyladenosine caused strong sedation [6].

High impact information on BRN 4888162

In contrast the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (0.01 to 1 microM) showed a 30% increase in PMA-stimulated adherence of neutrophils to endothelial cells [7].
On the other hand, 2-chloro-N6-cyclopentyladenosine (0.01 to 1 microM) did not significantly alter cAMP level in neutrophils and endothelial cells in the presence of 4(3-butoxy-4-methoxyphenyl)methyl)-2-imidazolidinone (Ro 20-1724) [7].
Pretreatment with either multiple episodes of ischemia or continuous infusion of a selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), resulted in attenuation of the protective effects of preconditioning, implying downregulation of the receptors involved in triggering classic preconditioning [8].
The rank order of potency was 2-chloro-N6-cyclopentyladenosine (IC50, 93 nM) greater than (R)-N6-phenylisopropyladenosine (IC50, 309 nM) greater than 5'-N-ethylcarboxamidoadenosine (IC50, 813 nM) much greater than (S)-N6-phenylisopropyladenosine (IC50, 26,300 nM) [9].
The selective adenosine A1 receptor agonists 2-chloro-N6-cyclopentyladenosine (CCPA; 0.1-0.4 microM) and R(-)N6-(2-phenylisopropyl)-adenosine (R-PIA; 1 microM) both depressed the EPSPm [10].

Biological context of BRN 4888162

Incubation of striatal synaptosomes with the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) caused the appearance of a low-affinity binding site for the A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) [11].
In both genotypes, the activation of A1 receptors by 2-chloro-N6-cyclopentyladenosine reduced the field excitatory postsynaptic potential (fEPSP) slope to a similar extent [12].
However, the adenosine A1 receptor agonists, R- and S-N6-(2-phenylisopropyl)adenosine, (R-PIA) and (S-PIA), N6-cyclohexyladenosine (CHA) and 2-chloro-N6-cyclopentyladenosine (CCPA), which stimulate adenylate cyclase and inhibit platelet aggregation in the low microM range, displaced [3H]CGS 21680 only in the high microM range [13].
The effects of hypoxia and Ado were reproduced by a specific A1 agonist (2-chloro-N6-cyclopentyladenosine), demonstrating impaired vasorelaxation induced by beta-AR stimulation in normoxia (70.6 +/- 4.5%, P < 0.01) [14].
In this study the effect of the A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA) on bis(1,3-diethylthiobarbituric acid)trimethine oxonol (bisoxonol)-monitored membrane potential in cerebrocortical nerve endings was evaluated [15].

Anatomical context of BRN 4888162

In particular, the A1 agonist 2-chloro-N6-cyclopentyladenosine can increase pulmonary resistance independently of mast cell activation [16].
Rabbits were pretreated with saline or the selective A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), 0.1 mg/kg i.v. After 24 h, they were anaesthetized and subjected to 30 min left coronary artery occlusion (CAO) and 120 min reperfusion [17].

Associations of BRN 4888162 with other chemical compounds

The A1 adenosine receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA, 0.3-2 microM), inhibited the respiratory rhythm, sPSCs, and enhanced activity of KATP channels [18].
The present work investigates the flexibility of this binding site by exhaustive exploration with the natural agonist and with three other adenosine derivatives: N6-cyclopentyladenosine (CPA), 2-chloro-N6-cyclopentyladenosine (CCPA), and 5'-N-ethylcarboxamidoadenosine (NECA) [19].
Rats were randomly assigned to 1 of 5 groups: (1) saline control (n = 13); (2) ischemic preconditioning (n = 6); (3) lidocaine only (608 microg . kg -1 . min -1 , n = 5); (4) adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 5 microg/kg, n = 7); and (5) CCPA plus lidocaine (n = 6) [20].
The effect of the adenosine receptor agonists, 2-chloro-N6-cyclopentyladenosine (CCPA) and 2-hexynyl-adenosine-5'-N-ethylcarboxamide (HENECA) on atrial natriuretic factor (ANF) release was investigated [21].

Gene context of BRN 4888162

RESULTS: After injection of the selective adenosine A1-receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of </=3.5 h after the injections [22].
The effect of the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) was investigated in CD1 mice by the elevated plus-maze and the light/dark test, two models for measuring anxiety in rodents [23].
The present study was undertaken to determine whether 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective A1 adenosine receptor agonist, attenuated cochlear dysfunction induced by transient ischemia or not [24].
The A2a receptor agonist carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at 10(-5) M attenuated the antiadrenergic effect of the selective A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), whereas CSC did not influence the antiadrenergic action of this agonist [25].
The pharmacological profile of 2-chloro-N6-cyclopentyladenosine (CCPA, CAS 37739-05-2), a highly selective A1 adenosine receptor agonist, was characterized [26].

Analytical, diagnostic and therapeutic context of BRN 4888162

We compared the effects of preconditioning induced by 2 cycles of 5 min of global ischemia and 2 cycles of 5 min of perfusion with either adenosine (100 mumol/L) or the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 100 nmol/L) in protecting against ischemia-induced arrhythmias in Langendorff-perfused rat hearts [27].

References

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Modeling hemodynamic profiles by telemetry in the rat. A study with A1 and A2a adenosine agonists. Bonizzoni, E., Milani, S., Ongini, E., Casati, C., Monopoli, A. Hypertension (1995) [Pubmed]
Delayed adenosine A1 receptor preconditioning in rat myocardium is MAPK dependent but iNOS independent. Lasley, R.D., Keith, B.J., Kristo, G., Yoshimura, Y., Mentzer, R.M. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
Cyclooxygenase-2 does not mediate late preconditioning induced by activation of adenosine A1 or A3 receptors. Kodani, E., Shinmura, K., Xuan, Y.T., Takano, H., Auchampach, J.A., Tang, X.L., Bolli, R. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
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Prolonging the delayed phase of myocardial protection: repetitive adenosine A1 receptor activation maintains rabbit myocardium in a preconditioned state. Dana, A., Baxter, G.F., Walker, J.M., Yellon, D.M. J. Am. Coll. Cardiol. (1998) [Pubmed]
Pharmacological characterization of the adenylate cyclase-coupled adenosine receptor in isolated guinea pig atrial myocytes. Wilken, A., Tawfik-Schlieper, H., Klotz, K.N., Schwabe, U. Mol. Pharmacol. (1990) [Pubmed]
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Desensitisation of the adenosine A1 receptor by the A2A receptor in the rat striatum. Dixon, A.K., Widdowson, L., Richardson, P.J. J. Neurochem. (1997) [Pubmed]
Inactivation of adenosine A2A receptor impairs long term potentiation in the accumbens nucleus without altering basal synaptic transmission. d'Alcantara, P., Ledent, C., Swillens, S., Schiffmann, S.N. Neuroscience (2001) [Pubmed]
Binding characteristics of the adenosine A2 receptor ligand [3H]CGS 21680 to human platelet membranes. Varani, K., Borea, P.A., Guerra, L., Dionisotti, S., Zocchi, C., Ongini, E. Biochem. Pharmacol. (1994) [Pubmed]
Adenosine A1-receptor mechanisms antagonize beta-adrenergic pulmonary vasodilation in hypoxia. McIntyre, R.C., Banerjee, A., Bensard, D.D., Brew, E.C., Hahn, A.R., Fullerton, D.A. Am. J. Physiol. (1994) [Pubmed]
The A1 agonist CCPA reduced bisoxonol-monitored membrane potential depolarization elicited by high K+ in cerebrocortical nerve endings. Amoroso, S., Iannotti, E., Saggese, M.L., Di Renzo, G., Annunziato, L. Biochim. Biophys. Acta (1995) [Pubmed]
In vivo role of the adenosine A3 receptor: N6-2-(4-aminophenyl)ethyladenosine induces bronchospasm in BDE rats by a neurally mediated mechanism involving cells resembling mast cells. Meade, C.J., Mierau, J., Leon, I., Ensinger, H.A. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
ATP-sensitive K+ channels mediate the delayed cardioprotective effect of adenosine A1 receptor activation. Baxter, G.F., Yellon, D.M. J. Mol. Cell. Cardiol. (1999) [Pubmed]
A1 adenosine receptors modulate respiratory activity of the neonatal mouse via the cAMP-mediated signaling pathway. Mironov, S.L., Langohr, K., Richter, D.W. J. Neurophysiol. (1999) [Pubmed]
Comparative analysis of putative agonist-binding modes in the human A1 adenosine receptor. Gutiérrez-de-Terán, H., Pastor, M., Centeno, N.B., Aqvist, J., Sanz, F. Chembiochem (2004) [Pubmed]
Pretreatment with an adenosine A1 receptor agonist and lidocaine: a possible alternative to myocardial ischemic preconditioning. Canyon, S.J., Dobson, G.P. J. Thorac. Cardiovasc. Surg. (2005) [Pubmed]
Release of atrial natriuretic factor induced by the A1 adenosine receptor agonist 2-chloro-N6-cyclopentyl-adenosine in the rat. Massi, M., Saija, A., Cristalli, G., Polidori, C., Perfumi, M., Costa, G. Pharmacol. Res. (1992) [Pubmed]
Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsy. Gouder, N., Fritschy, J.M., Boison, D. Epilepsia (2003) [Pubmed]
Adenosine A1 receptors modulate anxiety in CD1 mice. Florio, C., Prezioso, A., Papaioannou, A., Vertua, R. Psychopharmacology (Berl.) (1998) [Pubmed]
Effect of A1 adenosine receptor agonist upon cochlear dysfunction induced by transient ischemia. Tabuchi, K., Ito, Z., Wada, T., Takahashi, K., Hara, A., Kusakari, J. Hear. Res. (1999) [Pubmed]
Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart. Norton, G.R., Woodiwiss, A.J., McGinn, R.J., Lorbar, M., Chung, E.S., Honeyman, T.W., Fenton, R.A., Dobson, J.G., Meyer, T.E. Am. J. Physiol. (1999) [Pubmed]
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