Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of CPA (a selective A1 receptor agonist), NECA (a mixed A1 and A2 receptor agonist), and CGS 21680 (a selective A2 receptor agonist) on the ischemia-evoked release of gamma-aminobutyric acid (GABA) from rat cerebral cortex was investigated with the cortical cup technique. Cerebral ischemia (20 min) was elicited by four vessel occlusion. In control animals, superfusate GABA increased from a basal level of 206 +/- 26 nM (mean +/- S.E.M., n = 18) to 10,748 +/- 3,876 nM during the reperfusion period. Pretreatment with adenosine receptor agonists failed to affect basal levels of GABA release. However, CPA (10(-10) M), NECA (10(-9) M), and CGS 21680 (10(-8) M) significantly suppressed the ischemia-evoked release of GABA. The ability to block the ischemia-evoked release of GABA was not evident when the adenosine receptor agonists were administered at higher concentrations. Thus, the selective activation of either A1 or high-affinity A2a adenosine receptors results in an inhibition of ischemia-evoked GABA release.
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PMID:Adenosine receptor agonists inhibit the release of gamma-aminobutyric acid (GABA) from the ischemic rat cerebral cortex. 149 81

One hundred and eight patients were studied with fluid-filled oculoplethysmography and carotid phonoangiography (OPG-CPA) and by arteriography. Thirty-two patients also had "Doppler evaluation" of supraorbital arterial flow. The OPG-CPA correctly predicted the degree of occlusion in 76% of the involved vessels, including the degree of occlusion of each carotid for each patient (63%). The OPG-CPA identified at least one obstructing carotid lesion in 51 of the 56 (91%) patients with obstructing lesions demonstrated by arteriography. On a per patient basis, which requires that both carotids be correctly assessed, the OPG-CPA had a false negative rate of 9.6% and false positive rate of 50%. The supraorbital artery "Doppler evaluation" had an accuracy rate of 66%, a per patient false negative rate of 50%, and a per patient false positive rate of 12%. The OPG-CPA and supraorbital artery "Doppler evaluation" are adjunctive tests for evaluating patients with cerebral vascular insufficiency and should not, at present, replace arteriography in symptomatic patients or in certain asymptomatic patients.
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PMID:Use of combined oculoplethysmography, carotid phonoangiography and Doppler in the non-invasive diagnosis of extracranial carotid occlusive disease. 724 97

Selective adenosine receptor agonists and antagonists have marked effects on the outcome of cerebral ischemia, and adenosine receptors are expressed on astrocytes. In this study we examined the effects of various adenosine receptor agonists on the production of nitric oxide and the induction of iNOS in astrocytes activated by LPS/IFN-gamma and TNF-alpha/IL-1beta and on the production of TNF-alpha. Treatment of the cells with the A2A receptor agonist CGS 21680 inhibited both NO production and iNOS expression induced by stimulation with either LPS/IFN-gamma or TNF-alpha/IL-1beta, whereas the A1 and A3 receptor agonists, CPA and Cl-IB-MECA, respectively, did not have significant inhibitory effects. The inhibitory effect of the A2A receptor agonist was antagonized by the specific A2A receptor antagonist CSC. The A2A agonist also exerted a small inhibitory effect on the production of TNF-alpha. Similar inhibitory effects on the production of NO were obtained by cyclic AMP-elevating reagents, such as forskolin and dibutyryl cyclic AMP. Our findings suggest that activation of the A2A receptor inhibits NO production and iNOS expression likely via increased cAMP.
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PMID:Activation of the A2A adenosine receptor inhibits nitric oxide production in glial cells. 965 May 77

The synthesis and pharmacological profile of a series of neuroprotective adenosine agonists are described. Novel A(1) agonists with potent central nervous system effects and diminished influence on the cardiovascular system are reported and compared to selected reference adenosine agonists. The novel compounds featured are derived structurally from two key lead structures: 2-chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) and 2-chloro-N-(1-piperidinyl)adenosine (NNC 90-1515, 4). The agonists are characterized in terms of their in vitro profiles, both binding and functional, and in vivo activity in relevant animal models. Neuroprotective properties assessed after postischemic dosing in a Mongolian gerbil severe temporary forebrain ischemia paradigm, using hippocampal CA1 damage endpoints, and the efficacy of these agonists in an A(1) functional assay show similarities to some reference adenosine agonists. However, the new compounds we describe exhibit diminished cardiovascular effects in both anesthetized and awake rats when compared to reference A(1) agonists such as (R)-phenylisopropyladenosine (R-PIA, 5), N-cyclopentyladenosine (CPA, 2), 4, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR 79236, 26), N-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994, 27), and N-[(2-methylphenyl)methyl]adenosine (Metrifudil, 28). In mouse permanent middle cerebral artery occlusion focal ischemia, 2-chloro-N-[(R)-[(2-benzothiazolyl)thio]-2-propyl]adenosine (NNC 21-0136, 12) exhibited significant neuroprotection at the remarkably low total intraperitoneal dose of 0.1 mg/kg, a dose at which no cardiovascular effects are observed in conscious rats. The novel agonists described inhibit 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate-induced seizures, and in mouse locomotor activity higher doses are required to reach ED(50) values than for reference A(1) agonists. We conclude that two of the novel adenosine derivatives revealed herein, 12 and 5'-deoxy-5'-chloro-N-[4-(phenylthio)-1-piperidinyl]adenosine (NNC 21-0147, 13), representatives of a new series of P(1) ligands, reinforce the fact that novel selective adenosine A(1) agonists have potential in the treatment of cerebral ischemia in humans.
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PMID:N-substituted adenosines as novel neuroprotective A(1) agonists with diminished hypotensive effects. 1047 79

Selective A(1)adenosine receptor agonists produced a considerable neuroprotective effect during global cerebral ischemia. The neuroprotective effect decreased in the order: A(1)agonists-NECA-adenosine-A(2A)agonist CGS 21680, while selective A(3)adenosine receptor agonist was ineffective. Inhibitory analysis showed that A(1)adenosine receptors mediate the neuroprotective effect of CPA, are involved in the effects of NECA and adenosine (but not CGS 21680), and participate in natural resistance to cerebral ischemia. The role of A(2B)adenosine receptors in the realization of neuroprotective effects was also demonstrated.
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PMID:Role of adenosine receptors in neuroprotective effect during global cerebral ischemia. 1155 51

Comparative characteristics of a series of selective A1 agonists influencing the complex global cerebral ischemia (CGCI) are presented and the optimum conditions for realization of the neuroprotective effect are selected. The degree of the neuroprotective action blocking by theophylline and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) decreases in the following order: CPA CHA ADAC. The A1-receptor agonists exhibit both direct action upon brain (maximum for ADAC) and a peripheral mechanism (especially pronounced for CPA). There is a close correlation between the neuroprotective activity of the A1-receptor agonists and their hypothermal effect. It is suggested that the hypothermal action plays an important part in the neuroprotective activity of the A1-receptor agonists.
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PMID:[Comparative characteristics of A1-receptor agonists as neuroprotective agents]. 1176 92