Ap.sub.4 A as a hypotensive agent

Details Ap.sub.4 A as a hypotensive agent Ap.sub.4 A as a hypotensive agent

1993-02-25

1995-01-10

Rollins, John W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

536 2621, 536 2622, 514 46, A61K 3170

Patent

active

053807154

ABSTRACT:
A deliberated hypotensive agent is composed of diadenosine 5', 5'"-p.sup.1,p.sup.4 -tetraphosphate with formula (I) or a salt thereof for which administration is medically permissible in an effective amount: ##STR1##

REFERENCES:
patent: 3321463 (1967-05-01), Moffatt et al.
Luthje et al. (I), "Diadenosine Triphosphate (Ap.sub.3 A) Mediates Human Platelet Aggregation by Liberation of ADP," Biochem. Biophys. Res. Comm. 118(3), 704-709 (1984).
Luthje et al.(II), "Catabolism of Ap.sub.3 A and Ap.sub.4 A in Human Plasma," Eur. J. Biochem., 149, 119-127 (1985).
Blackburn et al., "Synthesis and Resistance to Enzymatic Hydrolysis of Stereochemically-Defined Phosphonate and Thiophosphate Analogues of P.sup.1, P.sup.4 -bis(5'-adenosyl)tetraphosphate," Nucleic Acids Research, 15(17), 6991-7004 (1987).
Harrison et al., "Inhibition of Platelet Aggregation and the Platelet Release Reaction by .alpha.,.omega.Diadenosine Polyphosphates," FEBS Letters, 54(1), 57-60 (1975).
Elmaleh et al., ".sup.99m Tc-labeled Nucleotides as Tumor-Seeking Radiodiagnostic Agents," Proc. Natl. Acad. Sci. USA, 81, 918-921 (1984).
"Metabolism of Diadenosine Tetraphosphate (Ap.sub.4 A)," Conference Abstracts published in Hoppe-Seyler's Z Physiol Chem., 365, S597-611 (1984).
Guranowski et al., "Phosphonate Analogues of Diadenosine 5', 5'"-Tetraphosphate as Substrates or Inhibitors of Procaryotic and Eucaryotic Enzymes Degrading Dinucleoside Tetraphosphates," Biochemistry, 26, 3425-3429 (1987).
Feldhaus et al., "Synthetic Inhibitors of Adenylase Kinase in the Assays for ATPases and Phosphokinases," Eur. J. Biochem., 57(1), 197-204 (1975); Chem. Abstr., 83:159.849u (1975); only Abstract provided.
Taursova et al., "The Synthesis of P.sup.1,P.sup.3 -bis(5'-Adenosyl)triphosphate, P.sup.1, P.sup.4 -bis(5'-Adenosyl)tetraphosphate and Its Phosphonate Analogues Using Carbonyl Derivatives on Nitrogen-Containing Heterocycles," Bioorg. Khim., 12(3), 404-407 (1986); Chem. Abstr., 105: 227,203e (1986); only Abstract provided.
Fukunaga et al., "Hypotensive Effects of Adenosine and Adenosine Triphosphate Compared with Sodium Nitroprusside," Anesthesia and Analgesia, 61, 273-278 (1982).
Busse et al., "Vasomotor Activity of Diadenosine Triphosphate and Diadenosine Tetraphosphate in Isolated Arteries," Am. J. Physiol., 254(5), H828-H832 (1988).
Nees, "Coronary Flow Increases Induced by Adenosine and Adenine Nucleotides Are Mediated by the Coronoray Endothelium: A New Principle of the Regulation of Coronary Flow," European Heart J., 10, Supplement F, 28-35 (1989).
"Martindale, The Extra Pharmacopoeia, 29th Ed." Reynolds et al. eds., The Pharmaceutical Press, London, 1989, at p. 1492, see entries for AMP (#9201-m) and ATP (#9203-v).
Sollevi et al., "Relationship Between Arterial and Venous Adenosine Levels and Vasodilation During ATP-and Adenosine Infusion in Dogs," Acta Physiol. Scand., 120, 171-176 (1984).

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