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Chemical Compound Review

Phenylguanide     1-(diaminomethylidene)-2- phenyl-guanidine

Synonyms: Lopac-P-120, Tocris-0969, CHEMBL13791, SureCN467623, Bio-0769, ...
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Disease relevance of P 1426

  • PBG injections also evoked hypotension, bradycardia, and sympathoinhibition.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
  • 2. PDG (5-16 micrograms kg-1) injected in the right atrium of twenty-six rats produced the classic pulmonary C fibre reflex: a vagally mediated, rapid onset of rapid shallow breathing, bradycardia and hypotension [2].
  • Agonists acting at 5-HT3 receptors (phenylbiguanide and 2-methyl-5-HT) had no effect on catalepsy [3].
  • These results suggest that the stimulation of pulmonary C-fibers via PBG injection can produce both inspiratory apnea and tachypnea [4].
  • These results show that (1) prolonged increase in RL measured after SO2 exposure does not result from a vagal reflex; (2) the cold-induced bronchospasm, as well as the bronchomotor response to PDG, are reduced or suppressed during the period where the effect of SO2 persisted [5].

Psychiatry related information on P 1426

  • On the basis of their response latencies following the right atrial injection of capsaicin or phenyldiguanide, the cells were classified as having their receptor endings within the reach of pulmonary (latency less than 3.5 s) or bronchial (latency above 3.5 s) circulation [6].
  • Intragastric pressure (IGP) as an index of gastric motor activity was used to investigate gastric motor responses elicited by phenyldiguanide (PDG) in rats under pentobarbitone anaesthesia [7].

High impact information on P 1426

  • Extracellular activity of neurons in the nucleus tractus solitarius (NTS) was recorded in response to bolus intra-atrial saline (50, 100, 200, or 300 microL) or phenylbiguanide (PBG, 16 micrograms/kg in 100 microL) administered in random sequence [1].
  • Intrapericardial pretreatment with the B2 receptor antagonist Hoe 140 completely inhibited the increases of blood pressure and renal sympathetic nerve activity in response to intrapericardial bradykinin but did not affect the responses to intrapericardial phenylbiguanide [8].
  • Displacement of the selective 5-HT3 receptor antagonist [3H]BRL 43694 by phenylbiguanide (PBG) derivatives revealed Ki values ranging from 3.4 x 10(-4) to 4.4 x 10(-10) M [9].
  • Ionophoretic application of PBG potentiated responses to vagus nerve and cardiopulmonary afferent stimulation, and granisetron significantly attenuated this cardiopulmonary input (20.2 +/- 5.7 to 10.6 +/- 4.1 spikes burst(-1)) in 9 of 10 neurones tested [10].
  • Similarly, intra-NTS GR205171 reversed partially or almost totally the inhibitory effect of local microinjections of phenylbiguanide, a 5-HT(3) receptor agonist, on baroreflex bradycardia induced either by phenylephrine administration or aortic nerve stimulation, respectively [11].

Chemical compound and disease context of P 1426


Biological context of P 1426

  • PBG administration evoked an increased activity in fourteen of the fifteen fibres tested, and the latencies of nine of these responses (1.3 +/- 0.5 s) were within the pulmonary circulation time [14].
  • In six neurones ionophoretic application of PBG (10-200 nA) depolarized the membrane and increased firing rate whilst in the other three neurones, PBG had no effect on membrane potential though it increased synaptic noise (n = 3) and firing rate (n = 2) [15].
  • MDL72222 (0.1 mg kg(-1), i.v.), a selective 5-HT(3) receptor antagonist, blocked the effects of PBG on arterial blood pressure, heart rate and presympathetic neuronal discharge [16].
  • Drugs such as cirazoline, guanoxan, naphazoline, tolazoline, clonidine, bromoxidine (UK 14,304) and phenylbiguanide displaced [3H]idazoxan from two distinct binding sites, which suggested the existence of two affinity states for I2-imidazoline sites that were not modulated by MgCl2 or the nucleotide analog guanylyl-5'-imido-diphosphate [17].
  • Consistent with earlier reports indicating that 5-HT1 and 5-HT2 receptor activity influences reproductive activity in a sex-dependent manner, PBG was found to facilitate male, but not female, rat sexual behavior [18].

Anatomical context of P 1426


Associations of P 1426 with other chemical compounds


Gene context of P 1426

  • Bilateral microinjection of the 5-HT3 receptor agonist, phenylbiguanide (1.7-5 nmol), produced an increase in blood pressure and reduced the cardiovagal component of the baroreflex [26].
  • When expressed in Xenopus oocytes, both variants individually formed 5-HT3 receptors that revealed no significant differences in current responses to the agonists 5-HT and 1-phenylbiguanide and block by the specific antagonist LY-278, 584-maleate [27].
  • In contrast, the level of endogenous AngII within the NTS appears to have variable effects on activation of cardiopulmonary vagal afferent fibres by phenylbiguanide [28].
  • Pulmonary vagal C-fibers were excited by right atrial injection of phenylbiguanide (PBG) while cardiac receptors were stimulated by left ventricular injection of veratridine (1-3 micrograms/kg) or mechanically by distension of the left ventricle (20-50 microl perfusate) using an indwelling cannula [29].
  • In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT2 or 5-HT3 receptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little suppressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, respectively, both P > 0.1 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)[30]

Analytical, diagnostic and therapeutic context of P 1426


  1. Responses of neurons in the nucleus tractus solitarius to stimulation of heart and lung receptors in the rat. Hines, T., Toney, G.M., Mifflin, S.W. Circ. Res. (1994) [Pubmed]
  2. Neurones in commissural nucleus tractus solitarii required for full expression of the pulmonary C fibre reflex in rat. Bonham, A.C., Joad, J.P. J. Physiol. (Lond.) (1991) [Pubmed]
  3. Behavioural effects of serotonin agonists and antagonists in the rat and marmoset. Elliott, P.J., Walsh, D.M., Close, S.P., Higgins, G.A., Hayes, A.G. Neuropharmacology (1990) [Pubmed]
  4. Pulmonary C-fibers elicit both apneusis and tachypnea in the rabbit. Matsumoto, S., Kanno, T., Yamasaki, M., Nagayama, T., Shimizu, T. Respiration physiology. (1992) [Pubmed]
  5. Interaction between SO2 and cold-induced bronchospasm in anesthetized rabbits. Barthélemy, P., Badier, M., Jammes, Y. Respiration physiology. (1988) [Pubmed]
  6. The medullary projections of afferent bronchopulmonary C fibres in the cat as shown by antidromic mapping. Kubin, L., Kimura, H., Davies, R.O. J. Physiol. (Lond.) (1991) [Pubmed]
  7. Motor reflexes of stomach elicited by phenyldiguanide in the rat. Rao, K.S. Can. J. Physiol. Pharmacol. (1980) [Pubmed]
  8. Epicardial bradykinin B2 receptors elicit a sympathoexcitatory reflex in rats. Veelken, R., Glabasnia, A., Stetter, A., Hilgers, K.F., Mann, J.F., Schmieder, R.E. Hypertension (1996) [Pubmed]
  9. Biguanide derivatives: agonist pharmacology at 5-hydroxytryptamine type 3 receptors in vitro. Morain, P., Abraham, C., Portevin, B., De Nanteuil, G. Mol. Pharmacol. (1994) [Pubmed]
  10. The role of central 5-HT3 receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats. Jeggo, R.D., Kellett, D.O., Wang, Y., Ramage, A.G., Jordan, D. J. Physiol. (Lond.) (2005) [Pubmed]
  11. Functional interaction between nucleus tractus solitarius NK1 and 5-HT3 receptors in the inhibition of baroreflex in rats. Comet, M.A., Laguzzi, R., Hamon, M., Sévoz-Couche, C. Cardiovasc. Res. (2005) [Pubmed]
  12. Histamine and phenyldiguanide induced tachypnea in hypercapnia and hypoxia. Miserocchi, G., Mazzarelli, M., Quinn, B., Mozes, R.S. Respiration physiology. (1979) [Pubmed]
  13. Medullary pathway of the Bezold-Jarisch reflex in the rat. Verberne, A.J., Guyenet, P.G. Am. J. Physiol. (1992) [Pubmed]
  14. Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats. Jones, J.F., Wang, Y., Jordan, D. J. Physiol. (Lond.) (1998) [Pubmed]
  15. Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal preganglionic neurones in anaesthetized rats. Wang, Y., Ramage, A.G., Jordan, D. J. Physiol. (Lond.) (1998) [Pubmed]
  16. Roles for CCK1 and 5-HT3 receptors in the effects of CCK on presympathetic vasomotor neuronal discharge in the rat. Saita, M., Verberne, A.J. Br. J. Pharmacol. (2003) [Pubmed]
  17. Discrimination and pharmacological characterization of I2-imidazoline sites with [3H]idazoxan and alpha-2 adrenoceptors with [3H]RX821002 (2-methoxy idazoxan) in the human and rat brains. Miralles, A., Olmos, G., Sastre, M., Barturen, F., Martin, I., Garcia-Sevilla, J.A. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  18. Effects of 5-HT3 agonists on reproductive behaviors in rats. Tanco, S.A., Watson, N.V., Gorzalka, B.B. Psychopharmacology (Berl.) (1994) [Pubmed]
  19. Non-NMDA receptors transmit cardiopulmonary C fibre input in nucleus tractus solitarii in rats. Wilson, C.G., Zhang, Z., Bonham, A.C. J. Physiol. (Lond.) (1996) [Pubmed]
  20. Activity of aortic chemoreceptors in the anaesthetized rat. Brophy, S., Ford, T.W., Carey, M., Jones, J.F. J. Physiol. (Lond.) (1999) [Pubmed]
  21. Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats. Wang, Y., Jones, J.F., Jeggo, R.D., de Burgh Daly, M., Jordan, D., Ramage, A.G. J. Physiol. (Lond.) (2000) [Pubmed]
  22. Effects of leptin on cat intestinal vagal mechanoreceptors. Gaigé, S., Abysique, A., Bouvier, M. J. Physiol. (Lond.) (2002) [Pubmed]
  23. Structure-activity relationships for the binding of arylpiperazines and arylbiguanides at 5-HT3 serotonin receptors. Dukat, M., Abdel-Rahman, A.A., Ismaiel, A.M., Ingher, S., Teitler, M., Gyermek, L., Glennon, R.A. J. Med. Chem. (1996) [Pubmed]
  24. Characterization of 5-HT3 receptors of N1E-115 neuroblastoma cells by use of the influx of the organic cation [14C]-guanidinium. Bönisch, H., Barann, M., Graupner, J., Göthert, M. Br. J. Pharmacol. (1993) [Pubmed]
  25. Behavioral effects of the 5-hydroxytryptamine3 receptor agonists 1-phenylbiguanide and m-chlorophenylbiguanide in rats. Higgins, G.A., Joharchi, N., Sellers, E.M. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  26. Cardiovascular effects of 5HT2 and 5HT3 receptor stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats. Merahi, N., Laguzzi, R. Brain Res. (1995) [Pubmed]
  27. Functional characterization of two 5-HT3 receptor splice variants isolated from a mouse hippocampal cell line. Glitsch, M., Wischmeyer, E., Karschin, A. Pflugers Arch. (1996) [Pubmed]
  28. Angiotensin peptides as neurotransmitters/neuromodulators in the dorsomedial medulla. Diz, D.I., Jessup, J.A., Westwood, B.M., Bosch, S.M., Vinsant, S., Gallagher, P.E., Averill, D.B. Clin. Exp. Pharmacol. Physiol. (2002) [Pubmed]
  29. Pattern of cardiorespiratory afferent convergence to solitary tract neurons driven by pulmonary vagal C-fiber stimulation in the mouse. Paton, J.F. J. Neurophysiol. (1998) [Pubmed]
  30. Modulation of light-induced C-Fos expression in the suprachiasmatic nuclei by 5-HT1A receptor agonists. Glass, J.D., Selim, M., Rea, M.A. Brain Res. (1994) [Pubmed]
  31. Impaired arterial baroreceptor reflex and cardiopulmonary vagal reflex in conscious spontaneously hypertensive rats. Widdop, R.E., Verberne, A.J., Jarrott, B., Louis, W.J. J. Hypertens. (1990) [Pubmed]
  32. Effects of levodropropizine on vagal afferent C-fibres in the cat. Shams, H., Daffonchio, L., Scheid, P. Br. J. Pharmacol. (1996) [Pubmed]
  33. Age-related effects of cardiac sympathetic denervation on the responses to cardiopulmonary receptor stimulation in piglets. Tong, S., Frasier, I.D., Ingenito, S., Sica, A.L., Gootman, N., Gootman, P.M. Pediatr. Res. (1997) [Pubmed]
  34. Carotid and cardiopulmonary chemoreceptor activity increases hippocampal theta rhythm in conscious rabbits. Yu, Y.H., Blessing, W.W. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2000) [Pubmed]
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