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Chemical Compound Review

ICYP     4-[2-hydroxy-3-(propan-2- ylamino)propoxy]...

Synonyms: AG-J-64291, AC1Q4PLW, CTK5F0774, AR-1C3628, LS-177759, ...
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Disease relevance of Iodocyanopindolol

  • Myocardial beta-adrenoceptors (125I-labeled iodocyanopindolol binding), Gi alpha (pertussis toxin labeling), Gs alpha-activity (reconstitution into cyc--S49 membranes) and adenylyl cyclase activity were measured [1].
  • We examined cardiac neuronal function and beta-receptor with a dual-tracer method of [(131)I]meta-iodobenzylguanidine (MIBG) and [(125)I]iodocyanopindolol (ICYP) in rat heart failure after myocardial infarction (MI) [2].
  • We show that R1.1, a murine thymoma cell line, possesses about 2,000 receptors per cell with high affinity for ICYP (kD = 3.3 X 10(-11) M) [3].
  • Isoproterenol competition for iodocyanopindolol binding was used to examine efficacy of receptor agonist interactions in myometrium from women at term, in labor, or before labor and from women in preterm labor [4].
  • Thus, in this study, changes in densities of alpha1- and beta2-adrenoceptors (alpha1-and beta2-ARs) were investigated in membranes of human liver with cholangiocarcinoma, and for comparison, in membranes of non-adjacent non-tumour liver using the potent antagonists [3H]-prazosin and [1I]-iodocyanopindolol (ICYP) respectively [5].

Psychiatry related information on Iodocyanopindolol

  • Values of binding maximum (Bmax) and dissociation constant (Kd) of (-)3-[125I]iodocyanopindolol (ICYP) were determined in beta-adrenergic receptors of membranes of peripheral lymphocytes in 32 patients with unipolar depression (DSM-III-R) and 31 normal controls [6].
  • We have investigated brain beta AR coupling in the frontal cortex, hippocampus and hypothalamus of rats exposed to inescapable shock and then tested for learned helplessness, and in both tested and naive controls using [125I]-iodocyanopindolol (ICYP) as the ligand [7].
  • At 15 days post-lesion, olfactory bulbectomized (OB) rats exhibited significant deficits in the acquisition of passive avoidance learning compared to sham lesioned rats. beta-Adrenoceptor binding in the amygdala, hippocampus and cerebral cortex was assayed with (-)-[125I]iodocyanopindolol (ICYP) [8].

High impact information on Iodocyanopindolol


Biological context of Iodocyanopindolol

  • Although purified membrane fractions all had ICYP binding characterized by a single binding site with similar Kd values, binding to some crude fractions was complex [14].
  • [125I]iodocyanopindolol (ICYP) autoradiography was used to investigate the temporal development and distribution of beta 1 and beta 2 receptors in brains of baboons at ages embryonic day 100 (E100), full-term gestation (El80), and 3 years [15].
  • Ten day exposure of animals to ethanol vapor (25 mg/l) in inhalation chambers had no effect on binding properties of antagonist iodocyanopindolol (ICYP) in either brain region [16].
  • Effect of age on the kinetics of the binding of iodocyanopindolol to a membrane preparation of rat lungs [17].

Anatomical context of Iodocyanopindolol

  • RESULTS: Binding of ICYP to transmural slices of hamster myocardium was rapid, saturable, stereoselective, and displaceable by antagonists [18].
  • Hamster and rat pineal gland beta-adrenoceptor characterization with iodocyanopindolol and the effect of decreased catecholamine synthesis on the receptor [19].
  • The nature of beta-adrenergic binding by swine corpora lutea and granulosa cells was examined with the specific beta-adrenergic radioligand, (+/-)3-[125I]iodocyanopindolol (ICYP) [20].
  • The binding of [125I]iodocyanopindolol (ICYP), a beta-adrenergic receptor antagonist, to membranes from human tracheal epithelial cells could be displaced by amiloride with IC50 = 410 microM; displacement was 70% at 10(-3) M amiloride [21].
  • A relatively new beta-adrenergic radioligand, 125I-iodocyanopindolol (ICP), was examined in binding assays with rat liver plasma membrane (LPM) [22].

Associations of Iodocyanopindolol with other chemical compounds

  • The IC50 values were (nmol/1) propranolol (non-selective) 24.8; ICI 118,551 (beta 2 selective) 14.7; CGP-12177 (non-selective) 28.9; bisoprolol (beta 1 selective) 1500; CGP-20712A (beta 1 selective) 8990. beta AR agonists displaced ICYP with a potency ranking isoprenaline greater than adrenaline greater than noradrenaline [23].
  • However, the highly beta-1-selective compound CGP 20712A was able to distinguish two binding sites on ICYP competition curves, a high-affinity "beta-1 site" (75%) and a low-affinity "beta-2 site" (25%) [24].
  • Despite the fact that beta receptor density was decreased by 50% in failing hearts (iodocyanopindolol Bmax 84.4 +/- 8.9 fmol/mg protein in nonfailing hearts vs 42.9 +/- 3.2 fmol/mg in failing hearts, P less than 0.01), dihydropyridine calcium antagonist binding sites were not reduced significantly by heart failure [25].
  • Binding of ICYP was shown by differential centrifugation and sucrose gradient purification as well as digitonin treatment to be directly related to the content of arterial muscle plasma membrane assessed by marker enzymes [14].
  • Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM [26].

Gene context of Iodocyanopindolol

  • The iodocyanopindolol and SM-11044 binding protein belongs to the TM9SF multispanning membrane protein superfamily [27].
  • A quantitative autoradiographic ICYP binding technique was also used to visualise atrial and ventricular beta adrenoceptors in heart sections [28].
  • 5-HT1B binding sites were visualized using [125I]iodocyanopindolol (ICYP) [29].
  • The total number of myocardial beta-adrenoceptors was assessed with the nonsubtype selective beta-adrenoceptor radioligand (-)[125I]iodocyanopindolol (ICYP); concomitantly, the number of beta 1-adrenoceptors was determined with the selective beta 1-adrenoceptor radioligand (-)[3H]bisoprolol [30].
  • Scatchard transformation of the data demonstrated high-affinity binding of ICYP to a single class of beta AR (Bmax = 80 +/- 10 fmol/mg protein; KD = 8 pM +/- 0.9; n = 8). beta AR antagonists displaced ICYP in a monophasic displacement pattern [23].

Analytical, diagnostic and therapeutic context of Iodocyanopindolol

  • The F(ab) fragments of 5B7 and R9 behaved in a similar manner, and the soluble complex responsible for the high-affinity interaction with ICYP can be identified by gel filtration chromatography [31].
  • Our observation of curvilinear Scatchard plots with (-)-[125I]iodocyanopindolol (ICYP) resulted in a re-evaluation of this radioligand and the influence of cell isolation techniques on leukocyte beta-adrenergic receptor binding parameters [32].
  • In addition, plasma membranes for mesenteric nerves, removed carefully by dissection in our study, were shown to contain ICYP binding sites with a similar Kd and Bmax values to those in arterial muscle membrane [14].
  • The affinity of ICYP to beta 2-adrenoceptors was not changed during or after treatment [33].
  • RESULTS: The Scatchard analysis of the ICYP-binding in both organs revealed no significant alterations in the dissociation constant (Kd) and in the maximal binding capacity (Bmax) between SHAM flight and control groups [34].


  1. Beta-adrenergic signal transduction following carvedilol treatment in hypertensive cardiac hypertrophy. Böhm, M., Ettelbrück, S., Flesch, M., van Gilst, W.H., Knorr, A., Maack, C., Pinto, Y.M., Paul, M., Teisman, A.C., Zolk, O. Cardiovasc. Res. (1998) [Pubmed]
  2. Heterogeneous cardiac sympathetic innervation in heart failure after myocardial infarction of rats. Igawa, A., Nozawa, T., Yoshida, N., Fujii, N., Inoue, M., Tazawa, S., Asanoi, H., Inoue, H. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  3. Reovirus type 3 and [125I]-iodocyanopindolol bind to distinct domains on the beta-adrenergic like receptor. Liu, J., Co, M.S., Greene, M.I. Immunol. Res. (1988) [Pubmed]
  4. Failure to demonstrate decreased beta-adrenergic receptor concentration or decreased agonist efficacy in term or preterm human parturition. Dattel, B.J., Lam, F., Roberts, J.M. Am. J. Obstet. Gynecol. (1986) [Pubmed]
  5. Alpha1-and beta2-adrenoceptors in the human liver with mass-forming intrahepatic cholangiocarcinoma: density and coupling to adenylate cyclase and phospholipase C. Kassahun, W.T., Günl, B., Tannapfel, A., Ungemach, F.R., Hauss, J., Abraham, G. Naunyn Schmiedebergs Arch. Pharmacol. (2005) [Pubmed]
  6. Lymphocyte beta-adrenoreceptor density in patients with unipolar depression and normal controls. Magliozzi, J.R., Gietzen, D., Maddock, R.J., Haack, D., Doran, A.R., Goodman, T., Weiler, P.G. Biol. Psychiatry (1989) [Pubmed]
  7. Indices of brain beta-adrenergic receptor signal transduction in the learned helplessness animal model of depression. Gurguis, G.N., Kramer, G., Petty, F. Journal of psychiatric research. (1996) [Pubmed]
  8. Differential effects of olfactory bulbectomy on beta-adrenoceptors in rat amygdala, hippocampus and cerebral cortex. Tiong, A.H., Richardson, J.S. Brain Res. (1990) [Pubmed]
  9. The interaction of verapamil and norverapamil with beta-adrenergic receptors. Feldman, R.D., Park, G.D., Lai, C.Y. Circulation (1985) [Pubmed]
  10. Characterization of a novel iodocyanopindolol and SM-11044 binding protein, which may mediate relaxation of depolarized rat colon tonus. Sugasawa, T., Matsuzaki-Fujita, M., Guillaume, J.L., Camoin, L., Morooka, S., Strosberg, A.D. J. Biol. Chem. (1997) [Pubmed]
  11. Molecular cloning and expression of the rat beta 1-adrenergic receptor gene. Machida, C.A., Bunzow, J.R., Searles, R.P., Van Tol, H., Tester, B., Neve, K.A., Teal, P., Nipper, V., Civelli, O. J. Biol. Chem. (1990) [Pubmed]
  12. Lymphocyte beta adrenoceptor upregulation and improved cardiac response to adrenergic stimulation following converting enzyme inhibition in congestive heart failure. Townend, J.N., Virk, S.J., Qiang, F.X., Lawson, N., Bain, R.J., Davies, M.K. Eur. Heart J. (1993) [Pubmed]
  13. Regulation of beta-adrenergic receptors on endothelial cells in culture. Graf, K., Gräfe, M., Dümmler, U., O'Connor, A., Regitz-Zagrosek, V., Kunkel, G., Auch-Schwelk, W., Fleck, E. Eur. Heart J. (1993) [Pubmed]
  14. Beta adrenoreceptor in vascular smooth muscle with special reference to subcellular localization and number of binding sites. Kwan, C.Y., Sipos, S.N., Osterroth, A., Daniel, E.E. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
  15. Development of beta 1 and beta 2 adrenergic receptors in baboon brain: an autoradiographic study using [125I]iodocyanopindolol. Slesinger, P.A., Lowenstein, P.R., Singer, H.S., Walker, L.C., Casanova, M.F., Price, D.L., Coyle, J.T. J. Comp. Neurol. (1988) [Pubmed]
  16. Effects of chronic exposure to ethanol alone and in combination with desipramine on beta-adrenoceptors of rat brain. Turkka, J., Gurguis, G., Karanian, J., Potter, W.Z., Linnoila, M. Eur. J. Pharmacol. (1990) [Pubmed]
  17. Effect of age on the kinetics of the binding of iodocyanopindolol to a membrane preparation of rat lungs. Fraeyman, N., Vanscheeuwijck, P. J. Recept. Res. (1991) [Pubmed]
  18. Augmentation of beta adrenergic receptors in cardiomyopathic hamsters (BIO 14.6) with heart failure. Tawarahara, K., Kurata, C., Taguchi, T., Kobayashi, A., Yamazaki, N. Cardiovasc. Res. (1992) [Pubmed]
  19. Hamster and rat pineal gland beta-adrenoceptor characterization with iodocyanopindolol and the effect of decreased catecholamine synthesis on the receptor. Craft, C.M., Morgan, W.W., Jones, D.J., Reiter, R.J. J. Pineal Res. (1985) [Pubmed]
  20. Properties of beta-adrenergic receptors on porcine corpora lutea and granulosa cells. Perkins, S.N., Cronin, M.J., Veldhuis, J.D. Endocrinology (1986) [Pubmed]
  21. Amiloride antagonizes beta-adrenergic stimulation of cAMP synthesis and Cl- secretion in human tracheal epithelial cells. Davis, P.B., Silski, C.L., Liedtke, C.M. Am. J. Respir. Cell Mol. Biol. (1992) [Pubmed]
  22. Age-related changes in the adrenergic control of glycogenolysis in rat liver: the significance of changes in receptor density. Bendeck, J.L., Noguchi, A. Pediatr. Res. (1985) [Pubmed]
  23. Binding of beta-adrenergic receptors in human skin. Steinkraus, V., Steinfath, M., Körner, C., Mensing, H. J. Invest. Dermatol. (1992) [Pubmed]
  24. Pharmacological characterization of chick and frog beta adrenergic receptors in primary cultures of myocardial cells. Port, J.D., Debellis, C.C., Klein, J., Peeters, G.A., Barry, W.H., Bristow, M.R. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  25. Calcium antagonist binding sites in failing and nonfailing human ventricular myocardium. Rasmussen, R.P., Minobe, W., Bristow, M.R. Biochem. Pharmacol. (1990) [Pubmed]
  26. Beta adrenoreceptors in the rabbit bladder detrusor muscle. Anderson, G.F., Marks, B.H. J. Pharmacol. Exp. Ther. (1984) [Pubmed]
  27. The iodocyanopindolol and SM-11044 binding protein belongs to the TM9SF multispanning membrane protein superfamily. Sugasawa, T., Lenzen, G., Simon, S., Hidaka, J., Cahen, A., Guillaume, J.L., Camoin, L., Strosberg, A.D., Nahmias, C. Gene (2001) [Pubmed]
  28. Specific atrial overexpression of G protein coupled human beta 1 adrenoceptors in transgenic mice. Bertin, B., Mansier, P., Makeh, I., Briand, P., Rostene, W., Swynghedauw, B., Strosberg, A.D. Cardiovasc. Res. (1993) [Pubmed]
  29. Sculpting the visual map: the distribution and function of serotonin-1A and serotonin-1B receptors in the optic tectum of the frog. Butt, C.M., Zhao, B., Duncan, M.J., Debski, E.A. Brain Res. (2002) [Pubmed]
  30. Regional distribution of beta-adrenoceptors in the human heart: coexistence of functional beta 1- and beta 2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy. Brodde, O.E., Schüler, S., Kretsch, R., Brinkmann, M., Borst, H.G., Hetzer, R., Reidemeister, J.C., Warnecke, H., Zerkowski, H.R. J. Cardiovasc. Pharmacol. (1986) [Pubmed]
  31. Enhanced antigen-antibody binding affinity mediated by an anti-idiotypic antibody. Sawutz, D.G., Koury, R., Homcy, C.J. Biochemistry (1987) [Pubmed]
  32. Effects of cell isolation procedures and radioligand selection on the characterization of human leukocyte beta-adrenergic receptors. Szefler, S.J., Edwards, C.K., Haslett, C., Zahniser, N.R., Miller, J.A., Henson, P.M. Biochem. Pharmacol. (1987) [Pubmed]
  33. Effects of beta-adrenoceptor antagonist administration on beta 2-adrenoceptor density in human lymphocytes. The role of the "intrinsic sympathomimetic activity". Brodde, O.E., Daul, A., Stuka, N., O'Hara, N., Borchard, U. Naunyn Schmiedebergs Arch. Pharmacol. (1985) [Pubmed]
  34. Biochemical characteristics of beta-adrenoceptors in rats after an 18-day spaceflight (LMS-STS78). Fagette, S., Somody, L., Bouzeghrane, F., Edward, K., Briggs, R., Viso, M., Gallo-Bon, N., Gharib, C., Gauquelin, G. Aviation, space, and environmental medicine. (1999) [Pubmed]
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