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Chemical Compound Review

SureCN27199     1,4-dihydropyridine

Synonyms: AGN-PC-00GT0V, AG-F-12473, AC1L2XKB, CTK1C4727, LS-174414, ...
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Disease relevance of Dihydropyridine


Psychiatry related information on Dihydropyridine


High impact information on Dihydropyridine

  • Genetic linkage analysis has localized the hypoKPP gene to chromosome 1q31-q32 near a dihydropyridine (DHP) receptor gene [1].
  • The source of calcium for BK channel activation is unknown, but the slow AHP is blocked by dihydropyridine antagonists, indicating that L-type calcium channels provide the calcium for activation of SK channels [11].
  • Here we report that the beta-subunit binds to the cytoplasmic linker between repeats I and II of the dihydropyridine-sensitive alpha 1-subunits from skeletal (alpha 1S) and cardiac muscles (alpha 1C-a), and also with the more distantly related neuronal alpha 1A and omega-conotoxin GVIA-sensitive alpha 1B-subunits [12].
  • The skeletal muscle dihydropyridine (DHP) receptor serves dual functions, as a voltage sensor for excitation-contraction coupling and as an L-type calcium channel [13].
  • The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged [14].

Chemical compound and disease context of Dihydropyridine


Biological context of Dihydropyridine


Anatomical context of Dihydropyridine

  • Structural and sequence similarities to the voltage-dependent sodium channel suggest that in the transverse tubule membrane of skeletal muscle the dihydropyridine receptor may act both as voltage sensor in excitation-contraction coupling and as a calcium channel [21].
  • The purified dihydropyridine-receptor complex has also been incorporated into phospholipid bilayer membranes [24].
  • As 3H-dihydropyridine binding to cortical membrane preparations resembles the binding in heart and smooth muscle where there are good functional correlates we conclude that the dihydropyridine binding sites in the brain represent functional Ca2+ channels that can be unmasked under certain circumstances [25].
  • There are dihydropyridine (DHP)-sensitive calcium currents in both skeletal and cardiac muscle cells, although the properties of these currents are very different in the two cell types (for simplicity, we refer to currents in both tissues as L-type) [26].
  • It is thought that in skeletal muscle excitation-contraction (EC) coupling, the release of Ca2+ from the sarcoplasmic reticulum is controlled by the dihydropyridine (DHP) receptor in the transverse tubular membrane, where it serves as the voltage sensor [27].

Associations of Dihydropyridine with other chemical compounds


Gene context of Dihydropyridine


Analytical, diagnostic and therapeutic context of Dihydropyridine


  1. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Ptácek, L.J., Tawil, R., Griggs, R.C., Engel, A.G., Layzer, R.B., Kwieciński, H., McManis, P.G., Santiago, L., Moore, M., Fouad, G. Cell (1994) [Pubmed]
  2. Calcium entry blockers in the treatment of hypertension. Current status and future prospects. Kaplan, N.M. JAMA (1989) [Pubmed]
  3. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. Agodoa, L.Y., Appel, L., Bakris, G.L., Beck, G., Bourgoignie, J., Briggs, J.P., Charleston, J., Cheek, D., Cleveland, W., Douglas, J.G., Douglas, M., Dowie, D., Faulkner, M., Gabriel, A., Gassman, J., Greene, T., Hall, Y., Hebert, L., Hiremath, L., Jamerson, K., Johnson, C.J., Kopple, J., Kusek, J., Lash, J., Lea, J., Lewis, J.B., Lipkowitz, M., Massry, S., Middleton, J., Miller, E.R., Norris, K., O'Connor, D., Ojo, A., Phillips, R.A., Pogue, V., Rahman, M., Randall, O.S., Rostand, S., Schulman, G., Smith, W., Thornley-Brown, D., Tisher, C.C., Toto, R.D., Wright, J.T., Xu, S. JAMA (2001) [Pubmed]
  4. Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons. Plummer, M.R., Logothetis, D.E., Hess, P. Neuron (1989) [Pubmed]
  5. Calcium currents recorded from a vertebrate presynaptic nerve terminal are resistant to the dihydropyridine nifedipine. Stanley, E.F., Atrakchi, A.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  6. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Forette, F., Seux, M.L., Staessen, J.A., Thijs, L., Babarskiene, M.R., Babeanu, S., Bossini, A., Fagard, R., Gil-Extremera, B., Laks, T., Kobalava, Z., Sarti, C., Tuomilehto, J., Vanhanen, H., Webster, J., Yodfat, Y., Birkenhäger, W.H. Arch. Intern. Med. (2002) [Pubmed]
  7. Unaltered hippocampal dihydropyridine and omega-conotoxin GVIA binding sites after repeated electroconvulsive shock in rats. Dooley, D.J. Biol. Psychiatry (1992) [Pubmed]
  8. The role of neuronal calcium channels in dependence on ethanol and other sedatives/hypnotics. Little, H.J. Pharmacol. Ther. (1991) [Pubmed]
  9. Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging. Yasar, S., Corrada, M., Brookmeyer, R., Kawas, C. Neurobiol. Aging (2005) [Pubmed]
  10. Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. Rejnmark, L., Vestergaard, P., Mosekilde, L. J. Hypertens. (2006) [Pubmed]
  11. Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Marrion, N.V., Tavalin, S.J. Nature (1998) [Pubmed]
  12. Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Pragnell, M., De Waard, M., Mori, Y., Tanabe, T., Snutch, T.P., Campbell, K.P. Nature (1994) [Pubmed]
  13. Function of a truncated dihydropyridine receptor as both voltage sensor and calcium channel. Beam, K.G., Adams, B.A., Niidome, T., Numa, S., Tanabe, T. Nature (1992) [Pubmed]
  14. Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel. Varadi, G., Lory, P., Schultz, D., Varadi, M., Schwartz, A. Nature (1991) [Pubmed]
  15. Coronary artery spasm in intact dogs induced by potassium and serotonin. Pérez, J.E., Saffitz, J.E., Gutiérrez, F.A., Henry, P.D. Circ. Res. (1983) [Pubmed]
  16. Nimodipine, a dihydropyridine-type calcium channel blocker, prevents alcoholic hepatitis caused by chronic intragastric ethanol exposure in the rat. Iimuro, Y., Ikejima, K., Rose, M.L., Bradford, B.U., Thurman, R.G. Hepatology (1996) [Pubmed]
  17. Vitamin D3 metabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. Caffrey, J.M., Farach-Carson, M.C. J. Biol. Chem. (1989) [Pubmed]
  18. Systemic and pulmonary hemodynamic responses to nicardipine during graded ergometric exercise in patients with moderate to severe essential hypertension. Cody, R.J., Kubo, S.H., Ryman, K.S., Shaknovich, A., Laragh, J.H. J. Am. Coll. Cardiol. (1987) [Pubmed]
  19. Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Staessen, J.A., Fagard, R., Thijs, L., Celis, H., Birkenhäger, W.H., Bulpitt, C.J., de Leeuw, P.W., Fletcher, A.E., Babarskiene, M.R., Forette, F., Kocemba, J., Laks, T., Leonetti, G., Nachev, C., Petrie, J.C., Tuomilehto, J., Vanhanen, H., Webster, J., Yodfat, Y., Zanchetti, A. Arch. Intern. Med. (1998) [Pubmed]
  20. Repeat I of the dihydropyridine receptor is critical in determining calcium channel activation kinetics. Tanabe, T., Adams, B.A., Numa, S., Beam, K.G. Nature (1991) [Pubmed]
  21. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Tanabe, T., Takeshima, H., Mikami, A., Flockerzi, V., Takahashi, H., Kangawa, K., Kojima, M., Matsuo, H., Hirose, T., Numa, S. Nature (1987) [Pubmed]
  22. Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA. Tanabe, T., Beam, K.G., Powell, J.A., Numa, S. Nature (1988) [Pubmed]
  23. Contributions of two types of calcium channels to synaptic transmission and plasticity. Edmonds, B., Klein, M., Dale, N., Kandel, E.R. Science (1990) [Pubmed]
  24. Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel. Flockerzi, V., Oeken, H.J., Hofmann, F., Pelzer, D., Cavalié, A., Trautwein, W. Nature (1986) [Pubmed]
  25. A functional correlate for the dihydropyridine binding site in rat brain. Middlemiss, D.N., Spedding, M. Nature (1985) [Pubmed]
  26. Cardiac-type excitation-contraction coupling in dysgenic skeletal muscle injected with cardiac dihydropyridine receptor cDNA. Tanabe, T., Mikami, A., Numa, S., Beam, K.G. Nature (1990) [Pubmed]
  27. Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling. Tanabe, T., Beam, K.G., Adams, B.A., Niidome, T., Numa, S. Nature (1990) [Pubmed]
  28. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Schramm, M., Thomas, G., Towart, R., Franckowiak, G. Nature (1983) [Pubmed]
  29. Neuropeptide modulation of single calcium and potassium channels detected with a new patch clamp configuration. Levitan, E.S., Kramer, R.H. Nature (1990) [Pubmed]
  30. Opening of dihydropyridine calcium channels in skeletal muscle membranes by inositol trisphosphate. Vilven, J., Coronado, R. Nature (1988) [Pubmed]
  31. Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis. Tricarico, D., Servidei, S., Tonali, P., Jurkat-Rott, K., Camerino, D.C. J. Clin. Invest. (1999) [Pubmed]
  32. Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. Monnier, N., Procaccio, V., Stieglitz, P., Lunardi, J. Am. J. Hum. Genet. (1997) [Pubmed]
  33. Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha 1, beta 1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect. Sudbrak, R., Golla, A., Hogan, K., Powers, P., Gregg, R., Du Chesne, I., Lehmann-Horn, F., Deufel, T. Hum. Mol. Genet. (1993) [Pubmed]
  34. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Dresser, G.K., Spence, J.D., Bailey, D.G. Clinical pharmacokinetics. (2000) [Pubmed]
  35. Roles of intracellular and extracellular calcium in the kinetic profile of adrenocorticotropin secretion by perifused rat anterior pituitary cells. II. Arginine vasopressin, oxytocin, and angiotensin-II stimulation. Won, J.G., Oki, Y., Orth, D.N. Endocrinology (1990) [Pubmed]
  36. Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell line. Tasaki, Y., Nakagawa, M., Ogata, J., Kiue, A., Tanimura, H., Kuwano, M., Nomura, Y. J. Urol. (1995) [Pubmed]
  37. Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes. White, R.E., Hartzell, H.C. Science (1988) [Pubmed]
  38. Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons. Mathie, A., Bernheim, L., Hille, B. Neuron (1992) [Pubmed]
  39. Subunit structure and localization of dihydropyridine-sensitive calcium channels in mammalian brain, spinal cord, and retina. Ahlijanian, M.K., Westenbroek, R.E., Catterall, W.A. Neuron (1990) [Pubmed]
  40. Localization of the alpha 1 and alpha 2 subunits of the dihydropyridine receptor and ankyrin in skeletal muscle triads. Flucher, B.E., Morton, M.E., Froehner, S.C., Daniels, M.P. Neuron (1990) [Pubmed]
  41. Dihydropyridine receptor gene expression is regulated by inhibitors of myogenesis and is relatively insensitive to denervation. Shih, H.T., Wathen, M.S., Marshall, H.B., Caffrey, J.M., Schneider, M.D. J. Clin. Invest. (1990) [Pubmed]
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