Antagonists stroke

Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J. Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 2000 31 347-354. 

Danysz W, Parsons CG, Mobius HJ, et al (2000) Neuroprotective and symptomatological action of memantine relevant for Alzheimer s disease—an unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2 85-97 Davis SM, Lees KR, Albers GW, et al (2000) Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 31 347-354 DeKeyser J (1991) Excitotoxic mechanisms may be involved in the pathophysiology of tardive dyskinesia. Clin Neuropharmacol 14 562-565 Del Dotto P, Pavese N, Gambaccini G, et al (2001) Intravenous amantadine improves levodopa-induced dyskinesias an acute double-blind placebo-controlled study. Mov Disord 16 515-520... 

Keywords Ionotropic receptors Co-agonism NMDA antagonists Glycine antagonists Stroke Pain Metabotropic receptors Epilepsy... 

Keywords NMDA Glycine antagonists Stroke Indole-2-carboxylates Benzoazepines Pyrido[2,3-()]pyrazines... 

Pyridazino[4,5-d]quinolinediones as novel glycine-V-methyl-D-aspartate antagonists for the treatment of stroke 98JHC1171. 

PI (adenosine) receptors were explored as therapeutic targets before P2 receptors. Adenosine was identified early and is in current use to treat supraventricular tachycardia. A2a receptor antagonists are being investigated for the treatment of Parkinson s disease and patents have been lodged for the application of PI receptor subtype agonists and antagonists for myocardial ischaemia and reperfusion injury, cerebral ischaemia, stroke, intermittent claudication and renal insufficiency. 

Abou-Chebl A, Bajzer CT, Krieger DW, Furlan AJ, Yadav JS. Multimodal therapy for the treatment of severe ischemic stroke combining GPEh/IIIa antagonists and angioplasty after failure of thrombolysis. Stroke 2005 36 2286-2288. 

Anakinra/Kineret, an IL-1 receptor antagonist approved for use in rheumatoid arthritis, was recently evaluated in a small phase II trial. When initiated within 6 hours after stroke onset, Anakinra treatment yielded promising preliminary results it was deemed safe with demonstrable biologic activity and likely favorable clinical outcome." ... 

Emsley HC, Smith CJ, Georgiou RF, Vail A, Hopkins SJ, RothweU NJ, Tyrrell PJ. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry 2005 76 1366-1372. 

Lyden PD, Jackson-Friedman C, Shin C, Hassid S. Synergistic combinatorial stroke therapy a quantal bioassay of a gaba agonist and a glutamate antagonist. Exp Neurol 2000 163 477 89. 

Zivin JA, Mazzarella V. Tissue plasminogen activator plus glutamate antagonist improves outcome after embolic stroke. Arch Neurol 1991 48 1235-1238. 

Trials of GP Ilb/IIIa Antagonists in Acute Ischemic Stroke... 

PROFESS is an ongoing large randomized trial examining combination ER-DP plus aspirin therapy compared with clopidogrel (each group also with or without telmisartan, an angiotensin receptor antagonist) for the secondary prevention of early and late recurrent stroke, and other vascular events. 

Junghans and Siebler reported a series of 24 patients with recent stroke or TIA due to LAA and detected ES on TCD who were treated acutely with intravenous tirofiban, a GP Ilb/IIIa receptor antagonist. Median ES rate at baseline was 38 signals per hour. ES were abolished by tirofiban in all patients, and returned following cessation of infusion. Although preliminary, these data support the rationale for trials of acute GP Ilb/IIIa receptor blockade in patients with recently symptomatic LAA awaiting CEA. 

Hypertension, or a chronic elevation in blood pressure, is a major risk factor for coronary artery disease congestive heart failure stroke kidney failure and retinopathy. An important cause of hypertension is excessive vascular smooth muscle tone or vasoconstriction. Prazosin, an aradrenergic receptor antagonist, is very effective in management of hypertension. Because oq-receptor stimulation causes vasoconstriction, drugs that block these receptors result in vasodilation and a decrease in blood pressure. 

Further new competitive AMPA antagonists include the imidazo-fused 23-benzodiazepine derivative 103. This compound showed excellent anticonvulsant activity and other activities indicative of possible therapeutic significance in human stroke and Parkinson k disease <00BMC2127>. An efficient synthesis of fluorine-containing H-1,4-diazepino[6,5-/t]quinolines has been described based on iV,/V-dimethyl-5,7-bis(trifluoroacetyl)-8-quinolylamine and an aromatic nucleophilic displacement with 1,2-ethylenediamine, followed by cyclocondensation <00S1822>. 

Palladium catalyzed cross coupling of arylboronic acid to nonracemic trifluoromethylsulfonyl and fluorosulfonyl enol ethers is one of the key steps in the synthesis two endothelin receptor antagonists, SB 209670 and SB 217242, which have been clinically evaluated for several illnesses including hypertension, ischemia, stroke and others [37] (Scheme 6.14). 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

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