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Chemical Compound Review

Lopac-G-110     2-[(2,6-dichlorophenyl) methylideneamino]gu...

Synonyms: Tocris-0885, SureCN15389, SureCN15390, BSPBio_002090, CAS-23256-50-0, ...
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Disease relevance of Wy 8678

  • Guanabenz, in some patients, is an effective monotherapy for the treatment of hypertension [1].
  • The data are consistent with selectively reduced renal sympathetic activity affecting sodium transport and provide a basis for the absence of edema and sodium retention associated with guanabenz therapy [2].
  • Four of the 5 non-arterial pressure-related neurons in the gigantocellular reticular nucleus, on the other hand, manifested no basic modification in their spike frequencies in relation to the hypotension induced by guanabenz [3].
  • Participation of nucleus reticularis gigantocellularis in guanabenz-promoted hypotension, decrease in cardiac contractility and bradycardia in rats [4].
  • They were produced by a lower dose per unit body weight in the rat whereas this was less marked for the alpha 2-adrenoceptor agonist guanabenz [5].

Psychiatry related information on Wy 8678

  • Clonidine (0.02-0.2 mg kg(-1) i.p.) and guanabenz (0.1-0.3 mg kg(-1) i.p.) induced amnesia in a dose-dependent manner [6].
  • The disposition of guanabenz, a centrally acting antihypertensive agent, was compared in 10 normotensive patients (eight males and two females) with chronic hepatic disease secondary to alcohol abuse and 10 healthy male volunteers after a 16 mg oral dose [7].
  • Conversion to guanabenz, a clonidine-like alpha 2 agonist, promptly relieved the opiate withdrawal symptoms without side effect recurrence [8].

High impact information on Wy 8678

  • Clonidine preserves RBF and GFR both acutely and chronically, guanabenz decreases RBF acutely but not chronically, and alpha-methyl dopa preserved RBF but decreases GFR [9].
  • Conscious rats with CHF showed elevated plasma catecholamines and enhanced responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to air stress and to intracerebroventricular (ICV) injection of the alpha 2-adrenergic receptor agonist guanabenz compared with sham-operated rats [10].
  • Intracerebroventricular preinjection of 0.3 microgram ouabain significantly enhanced blood pressure and RSNA responses to air stress and intracerebroventricular guanabenz in Dahl S rats given regular sodium to the levels observed in Dahl S rats given high sodium [11].
  • Similarly, ICI 118,551 administered into the lateral hypothalamus or lateral cerebral ventricle, or guanabenz (alpha 2-adrenoceptor agonist) given into the posterior hypothalamus, had no effects on the renal or mean arterial pressure responses to air stress [12].
  • Guanabenz therapy had no significant natriuretic or antinatriuretic effects in patients with an effective BP decrease, although it had the ability to produce and sustain a water diuresis [1].

Chemical compound and disease context of Wy 8678


Biological context of Wy 8678


Anatomical context of Wy 8678


Associations of Wy 8678 with other chemical compounds


Gene context of Wy 8678


Analytical, diagnostic and therapeutic context of Wy 8678

  • A single dose of guanabenz was examined for effects upon blood pressure, heart rate, plasma catecholamines, and plasma renin activity in a randomized, double-blind, crossover design [30].
  • Surgical renal denervation or pretreatment with an alpha 2-adrenergic receptor antagonist (rauwolscine, 30 micrograms i.c.v.) attenuated the ability of guanabenz to inhibit renal sympathetic nerve activity or increase urinary sodium excretion in SHR and WKY on either normal or high sodium intake [31].
  • Furthermore, [123I]MIBG scintigraphy after oral administration of an alpha 2 agonist (guanabenz acetate; 4 mg) demonstrated that myocardial uptake and clearance of MIBG returned to normal, as did the %LF [32].
  • Administration of the selective alpha-2 adrenergic receptor agonists B-HT 933 (2-20 nmol) and guanabenz (1.7-17 nmol) into the kidney produced only small increases in PG output and perfusion pressure, whereas another selective alpha-2 adrenergic receptor agonist xylazine (1-20 nmol) failed to increase perfusion pressure or PG output [33].
  • Microinjection of guanabenz directly into the ventro-medial portion of the nucleus reticularis gigantocellularis, at an ineffective systemic concentration (500 ng), produced significant and prolonged reduction in arterial pressure, cardiac contractility and heart rhythm [4].


  1. Effects of guanabenz therapy on renal function and body fluid composition. Bauer, J.H. Arch. Intern. Med. (1983) [Pubmed]
  2. Guanabenz: a centrally acting, natriuretic antihypertensive drug. Gehr, M., MacCarthy, E.P., Goldberg, M. Kidney Int. (1986) [Pubmed]
  3. Correlated effects of guanabenz on single-neuron activity in the nucleus reticularis gigantocellularis, systemic arterial pressure and heart rate in the rat. Chan, S.H., Lin, A.M. Neuropharmacology (1988) [Pubmed]
  4. Participation of nucleus reticularis gigantocellularis in guanabenz-promoted hypotension, decrease in cardiac contractility and bradycardia in rats. Lim, H.C., Chong, O.K., Chan, S.H. Neuropharmacology (1985) [Pubmed]
  5. Difference in the potency of alpha 2-adrenoceptor agonists and antagonists between the pithed rabbit and rat. Bulloch, J.M., Docherty, J.R., Flavahan, N.A., McGrath, J.C., McKean, C.E. Br. J. Pharmacol. (1987) [Pubmed]
  6. Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype. Galeotti, N., Bartolini, A., Ghelardini, C. Behav. Brain Res. (2004) [Pubmed]
  7. Pharmacokinetics of guanabenz in patients with impaired liver function. Lasseter, K.C., Shapse, D., Pascucci, V.L., Chiang, S.T. J. Cardiovasc. Pharmacol. (1984) [Pubmed]
  8. Guanabenz therapy for opiate withdrawal. Mulry, J.T. Drug intelligence & clinical pharmacy. (1985) [Pubmed]
  9. Antiadrenergic antihypertensive drugs: their effect on renal function. Bernstein, K.N., O'Connor, D.T. Annu. Rev. Pharmacol. Toxicol. (1984) [Pubmed]
  10. Brain 'ouabain' mediates sympathetic hyperactivity in congestive heart failure. Leenen, F.H., Huang, B.S., Yu, H., Yuan, B. Circ. Res. (1995) [Pubmed]
  11. Brain "ouabain" mediates the sympathoexcitatory and hypertensive effects of high sodium intake in Dahl salt-sensitive rats. Huang, B.S., Leenen, F.H. Circ. Res. (1994) [Pubmed]
  12. Hypothalamic beta 2-adrenoceptor control of renal sympathetic nerve activity and urinary sodium excretion in conscious, spontaneously hypertensive rats. Koepke, J.P., Jones, S., DiBona, G.F. Circ. Res. (1986) [Pubmed]
  13. Role of potassium channels in the antinociception induced by agonists of alpha2-adrenoceptors. Galeotti, N., Ghelardini, C., Vinci, M.C., Bartolini, A. Br. J. Pharmacol. (1999) [Pubmed]
  14. ANG II in median preoptic nucleus and pressor responses to CSF sodium and high sodium intake in SHR. Budzikowski, A.S., Leenen, F.H. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  15. Effect of guanabenz and hydrochlorothiazide on blood pressure and plasma renin activity. Holland, O.B., Fairchild, C., Gomez-Sanchez, C.E. Journal of clinical pharmacology. (1981) [Pubmed]
  16. Comparative antihypertensive effects of guanabenz and methyldopa. Walker, B.R., Deitch, M.W., Schneider, B.E., Hare, L.E. Clinical therapeutics. (1981) [Pubmed]
  17. Both brain angiotensin II and "ouabain" contribute to sympathoexcitation and hypertension in Dahl S rats on high salt intake. Huang, B.S., Leenen, F.H. Hypertension (1998) [Pubmed]
  18. Renal sympathetic neural mechanisms as intermediate phenotype in spontaneously hypertensive rats. DiBona, G.F., Jones, S.Y., Sawin, L.L. Hypertension (1996) [Pubmed]
  19. Selective central alpha-2 adrenoceptor control of regional haemodynamic responses to air jet stress in conscious spontaneously hypertensive rats. Kapusta, D.R., Knardahl, S., Koepke, J.P., Johnson, A.K., DiBona, G.F. J. Hypertens. (1989) [Pubmed]
  20. Central imidazoline (I1) receptors as targets of centrally acting antihypertensives: moxonidine and rilmenidine. van Zwieten, P.A. J. Hypertens. (1997) [Pubmed]
  21. Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Erb, S., Hitchcott, P.K., Rajabi, H., Mueller, D., Shaham, Y., Stewart, J. Neuropsychopharmacology (2000) [Pubmed]
  22. Renal effects of infusion of rilmenidine and guanabenz in conscious dogs: contribution of peripheral and central nervous system alpha 2-adrenoceptors. Evans, R.G., Anderson, W.P. Br. J. Pharmacol. (1995) [Pubmed]
  23. Sympathetic and parasympathetic nerves regulate postsynaptic alpha-2 adrenoceptor in salivary glands. Kaniucki, M.D., Elverdin, J.C., Luchelli-Fortis, M.A., Perec, C.J., Stefano, F.J. J. Pharmacol. Exp. Ther. (1986) [Pubmed]
  24. Novel hypotensive agents from Verbesina caracasana: structure, synthesis and pharmacology. Botta, B., Carmignani, M., Volpe, A.R., Botta, M., Corelli, F., Delle Monache, G. Current medicinal chemistry. (2003) [Pubmed]
  25. Protective effects of rilmenidine and AGN 192403 on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes. Choi, D.H., Kim, D.H., Park, Y.G., Chun, B.G., Choi, S.H. Free Radic. Biol. Med. (2002) [Pubmed]
  26. Enhanced sympathoexcitatory and pressor responses to central Na+ in Dahl salt-sensitive vs. -resistant rats. Huang, B.S., Wang, H., Leenen, F.H. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  27. Formation of guanoxabenz from guanabenz in human liver. A new metabolic marker for CYP1A2. Clement, B., Demesmaeker, M. Drug Metab. Dispos. (1997) [Pubmed]
  28. Multiple alpha-2 adrenergic receptor subtypes. II. Evidence for a role of rat R alpha-2A adrenergic receptors in the control of nociception, motor behavior and hippocampal synthesis of noradrenaline. Millan, M.J., Bervoets, K., Rivet, J.M., Widdowson, P., Renouard, A., Le Marouille-Girardon, S., Gobert, A. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  29. The antiinflammatory action of guanabenz is mediated through 5-lipoxygenase and cyclooxygenase inhibition. Chang, J., Blazek, E., Skowronek, M., Marinari, L., Carlson, R.P. Eur. J. Pharmacol. (1987) [Pubmed]
  30. Effect of guanabenz on blood pressure responses to posture and exercise. Dziedzic, S.W., Elijovich, F., Felton, K., Yeager, K., Krakoff, L.R. Clin. Pharmacol. Ther. (1983) [Pubmed]
  31. Sodium responsiveness of central alpha 2-adrenergic receptors in spontaneously hypertensive rats. Koepke, J.P., Jones, S., DiBona, G.F. Hypertension (1988) [Pubmed]
  32. Abnormal iodine-123-MIBG images in healthy volunteers. Morozumi, T., Fukuchi, K., Uehara, T., Kusuoka, H., Hori, M., Nishimura, T. J. Nucl. Med. (1996) [Pubmed]
  33. Prostaglandin synthesis and renal vasoconstriction elicited by adrenergic stimuli are linked to activation of alpha-1 adrenergic receptors in the isolated rat kidney. Cooper, C.L., Malik, K.U. J. Pharmacol. Exp. Ther. (1985) [Pubmed]
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