hexamethonium

Summary

Summary: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.

Top Publications

  1. Savulescu J, Spriggs M. The hexamethonium asthma study and the death of a normal volunteer in research. J Med Ethics. 2002;28:3-4 pubmed
  2. Yasuda M, Izumi H. Trigeminal nerve-mediated reflex arterial blood pressure decrease and vasodilatation in lower lip of the rabbit. Brain Res. 2003;987:59-66 pubmed
    ..Prior administration of hexamethonium at 10 mg/kg markedly reduced both the ipsilateral LBF increase and arterial blood pressure decrease, although ..
  3. de Man J, Moreels T, de Winter B, Bogers J, Van Marck E, Herman A, et al. Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum. Br J Pharmacol. 2001;133:695-707 pubmed
    ..b>Hexamethonium (100 microM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum ..
  4. DeNoble V, Mele P. Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone. Psychopharmacology (Berl). 2006;184:266-72 pubmed
    ..5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c...
  5. Karavaev E, Popova I, Kichigina V. The nicotinic receptor blocker hexamethonium alters neuronal responses to glutamate in the medial septal area of the brain of the ground squirrel in vitro. Neurosci Behav Physiol. 2008;38:297-307 pubmed publisher
    ..used to study the influences of L-glutamate (1 microM) during application of the nicotinic receptor blocker hexamethonium (1 mM)...
  6. Redai I, Richards K, England A, Feldman S. Interaction of decamethonium with hexamethonium or vecuronium in the rat: an isobolographic analysis. Anesth Analg. 1995;81:768-72 pubmed
    We used isobolographic analysis to investigate the interaction of decamethonium with either hexamethonium or vecuronium in the rat phrenic nerve hemidiaphragm preparation...
  7. Allen A, Dampney R, Mendelsohn F. Angiotensin receptor binding and pressor effects in cat subretrofacial nucleus. Am J Physiol. 1988;255:H1011-7 pubmed
    ..increase in arterial pressure, which was abolished by systemic administration of the ganglion-blocking drug hexamethonium bromide. In contrast, microinjections just outside the SRF nucleus had no effect on arterial pressure...
  8. de La Coussaye J, Eledjam J, Bruelle P, Lefrant J, Bassoul B, Peray P, et al. Mechanisms of the putative cardioprotective effect of hexamethonium in anesthetized dogs given a large dose of bupivacaine. Anesthesiology. 1994;80:595-605 pubmed
    ..This is based in part on the fact that hexamethonium suppresses cardiac disturbances in anesthetized rabbits given small intracerebroventricular doses of ..
  9. Barreto S, Woods C, Carati C, Schloithe A, Jaya S, Toouli J, et al. Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin. Am J Physiol Gastrointest Liver Physiol. 2009;297:G333-9 pubmed publisher
    ..Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), hexamethonium (10(-5) M), or diazoxide (10(-7) M and 10(-4) M) for 30 min followed by incubation with caerulein (10(-10) M) ..

More Information

Publications62

  1. Komine H, Matsukawa K, Tsuchimochi H, Nakamoto T, Murata J. Sympathetic cholinergic nerve contributes to increased muscle blood flow at the onset of voluntary static exercise in conscious cats. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1251-62 pubmed publisher
    ..Both a sympathetic ganglionic blocker (hexamethonium bromide) and atropine sulfate or methyl nitrate blunted the increase in brachial vascular conductance at the ..
  2. Dunn S, Raftery M. Cholinergic binding sites on the pentameric acetylcholine receptor of Torpedo californica. Biochemistry. 1993;32:8608-15 pubmed
    ..abstract truncated at 250 words)..
  3. Chen X, Patel K, Connors S, Mendonca M, Welch W, Wilcox C. Acute antihypertensive action of Tempol in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2007;293:H3246-53 pubmed
    ..methyl ester (L-NAME), and by 40% by the blockade of ganglionic autonomic neurotransmission with hexamethonium. L-NAME and hexamethonium were additive, but glibenclamide and hexamethonium were less than additive...
  4. Casais M, Delgado S, Sosa Z, Rastrilla A. Pregnancy in rats is modulated by ganglionic cholinergic action. Reproduction. 2006;131:1151-8 pubmed
    ..Thus, we conclude that the cholinergic sympathetic system from the celiac ganglion might be a fine modulator of the pregnancy physiology...
  5. Manintveld O, te Lintel Hekkert M, Keijzer E, Verdouw P, Duncker D. Intravenous adenosine protects the myocardium primarily by activation of a neurogenic pathway. Br J Pharmacol. 2005;145:703-11 pubmed
    ..05 vs ADO, P = NS vs LNNA). The ganglion blocker hexamethonium, which had also no effect on IS (IS = 66 +/- 3%), blunted the protection by ADO (IS = 55 +/- 4%; P < 0...
  6. Spring C, Mevissen M, Reist M, Zulauf M, Steiner A. Modification of spontaneous contractility of smooth muscle preparations from the bovine abomasal antrum by serotonin receptor agonists. J Vet Pharmacol Ther. 2003;26:377-85 pubmed
    ..Blockade of 5-HT2-induced response was tested with atropine and hexamethonium. Serotonin evoked a significant increase in the area under curve (AUC), whilst the 5-HT2 receptor agonist ..
  7. Hayashi K, Shibata C, Nagao M, Sato M, Kakyo M, Kinouchi M, et al. Intracolonic capsaicin stimulates colonic motility and defecation in conscious dogs. Surgery. 2010;147:789-97 pubmed publisher
    ..The aim of this study was to investigate the effects of intracolonic capsaicin on colonic motility and defecation...
  8. Hawkins B, Egleton R, Davis T. Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors. Am J Physiol Heart Circ Physiol. 2005;289:H212-9 pubmed
    ..barrier-permeant nicotinic antagonist mecamylamine and the blood-brain barrier-impermeant nicotinic antagonist hexamethonium to 0.5 +/- 0.2 and 0.3 +/- 0.2 microl.g(-1).min(-1), respectively...
  9. Gooz M, Toth M, Vakkuri O, Gooz P, Smolka A, de Châtel R, et al. Endogenous ouabain-like factor (OLF) secretion is modulated by nicotinic mechanisms in rat adrenocortical cells. Life Sci. 2004;74:2111-28 pubmed
    ..The ganglionic blockers hexamethonium and mecamylamine further potentiated the effect of nicotine, implicating nicotinic acetylcholine receptors (..
  10. Soto C, Ortiz F, Vargas R, Arroyo J, Alcayaga J. Responses induced by acetylcholine and ATP in the rabbit petrosal ganglion. Respir Physiol Neurobiol. 2010;172:114-21 pubmed publisher
    ..Acetylcholine-induced responses were mimicked by nicotine, antagonized by hexamethonium, and enhanced by atropine...
  11. Tsukimi Y, Mizuyachi K, Yamasaki T, Niki T, Hayashi F. Cold response of the bladder in guinea pig: involvement of transient receptor potential channel, TRPM8. Urology. 2005;65:406-10 pubmed
    ..To address the physiologic role of TRPM8, one of the transient receptor potential channels, we investigated the bladder cooling reflex and the effect of menthol on it in the guinea pig...
  12. Bian X, Bornstein J, Bertrand P. Nicotinic transmission at functionally distinct synapses in descending reflex pathways of the rat colon. Neurogastroenterol Motil. 2003;15:161-71 pubmed
    ..b>Hexamethonium (200 micromol L(-1)) in the recording chamber abolished reflexly evoked IJPs, while in the stimulation chamber,..
  13. Spencer N, Hennig G, Smith T. A rhythmic motor pattern activated by circumferential stretch in guinea-pig distal colon. J Physiol. 2002;545:629-48 pubmed
    ..EJPs and IJPs were abolished by hexamethonium (300 microM) or tetrodotoxin (1 microM), but persisted in the presence of pyridoxal phosphate-6-azophenyl-2',4'..
  14. Kofke W, Garman R, Janosky J, Rose M. Opioid neurotoxicity: neuropathologic effects in rats of different fentanyl congeners and the effects of hexamethonium-induced normotension. Anesth Analg. 1996;83:141-6 pubmed
    We tested the hypotheses that convulsant doses of opioids would produce limbic system damage exacerbated by hexamethonium. Ventilated paralyzed rats received intravenous (IV) isovolumic infusion of fentanyl loading dose (LD) 1000 ..
  15. Yuyama N, Mizuno J, Tsuzuki H, Wada Takahashi S, Takahashi O, Tamura K. Effects of extrinsic autonomic inputs on expression of c-Fos immunoreactivity in myenteric neurons of the guinea pig distal colon. Brain Res. 2002;948:8-16 pubmed
    ..Application of tetrodotoxin (0.2 microM) abolished the expression of c-Fos-immunoreactivity (n=6), but hexamethonium (100 microM) failed to decrease the number of c-Fos-positive neurons despite a complete suppression of ..
  16. Yang Y, Chang K, Chen C, Chiu T. Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor. Chin J Physiol. 2000;43:23-8 pubmed
    ..antagonized by the muscarinic receptor antagonist, atropine, but not by the nicotinic receptor antagonist, hexamethonium. Methoctramine, a selective M2-muscarinic receptor antagonist, was also effective in reversing the arecoline-..
  17. Takanashi H, Yogo K, Ozaki K, Koga H, Itoh Z, Omura S. In vitro pharmacological characterization of mitemcinal (GM-611), the first acid-resistant non-peptide motilin receptor agonist, in smooth muscle of rabbit small intestine. Pharmacology. 2007;79:137-48 pubmed
    ..contractile responses to mitemcinal or pMTL were not affected by pretreatment with atropine, tetrodotoxin, hexamethonium, naloxone or tropisetron...
  18. Castiglioni P, Di Rienzo M, Radaelli A. Effects of autonomic ganglion blockade on fractal and spectral components of blood pressure and heart rate variability in free-moving rats. Auton Neurosci. 2013;178:44-9 pubmed publisher
    ..BP was recorded in 11 rats before and after autonomic blockade by hexamethonium infusion (HEX). Systolic and diastolic BP, pulse pressure and pulse interval were derived beat-by-beat...
  19. Shomrat T, Graindorge N, Bellanger C, Fiorito G, Loewenstein Y, Hochner B. Alternative sites of synaptic plasticity in two homologous "fan-out fan-in" learning and memory networks. Curr Biol. 2011;21:1773-82 pubmed publisher
  20. Nelson M, Debas H, Mulvihill S. Vagal stimulation of rat exocrine pancreatic secretion occurs via multiple mediators. Gastroenterology. 1993;105:221-8 pubmed
  21. Yeoman M, Parish D, Benjamin P. A cholinergic modulatory interneuron in the feeding system of the snail, Lymnaea. J Neurophysiol. 1993;70:37-50 pubmed
    ..Less specific cholinergic antagonists blocked either excitatory (hexamethonium, 10(-4) M) or both excitatory and inhibitory connections (d-tubo-curarine, 10(-4) M). 6...
  22. Ishii H, Niioka T, Izumi H. Difference between male and female rats in cholinergic activity of parasympathetic vasodilatation in the masseter muscle. Arch Oral Biol. 2009;54:533-42 pubmed publisher
    ..since these increases were profoundly reduced by pretreatment with the autonomic cholinergic ganglion blocker hexamethonium (10 mg/kg)...
  23. Watanabe H, Ishii H, Niioka T, Yamamuro M, Izumi H. Occurrence of parasympathetic vasodilator fibers in the lower lip of the guinea-pig. J Comp Physiol B. 2008;178:297-305 pubmed
    ..the lip blood flow evoked by lingual nerve stimulation in guanethidine pretreated guinea-pigs were reduced by hexamethonium (an autonomic ganglion cholinergic blocker) in a dose-dependent manner...
  24. Tang F, Wong M, Hwang I, Li Y. Ether stress increases adrenomedullin gene expression and levels in the rat adrenal. Horm Metab Res. 2005;37:585-8 pubmed
    ..mRNA levels were increased after stress, and this effect was not blocked by pretreatment with hexamethonium. We conclude that stress increases adrenomedullin synthesis and secretion from the adrenal medulla through a ..
  25. Teranishi Y, Tsuru H, Shimomura H, Amano T, Matsubayashi H. Compensatory vasoconstrictor effects of sodium pentobarbital on the hindquarters of conscious normotensive control and lumbar-sympathectomized Wistar rats. Auton Neurosci. 2000;82:130-6 pubmed
    ..and a decrease in MAP (-17.0 +/- 3.2%). After pentobarbital anesthesia, subsequent ganglionic blockade with hexamethonium bromide (C6; 25 mg, i.v.) induced a significant decrease in HQR (-30.9 +/- 3...
  26. das Neves J, Hackl L, Freitas C, Paschoalini M, Marino Neto J. Central injections of noradrenaline and adrenaline differentially affect plasma free fatty acid and glucose in conscious pigeons (Columba livia). J Comp Physiol B. 2000;170:379-86 pubmed
    ..of adrenaline and noradrenaline was investigated by systemic pretreatment with a ganglionic blocker (hexamethonium, 1 mg/100 g), guanethidine (5 mg/100 g), and somatostatin (15 microg/100 g), respectively, 15 min before ..
  27. Sorensson J, Jodal M, Lundgren O. Involvement of nerves and calcium channels in the intestinal response to Clostridium difficile toxin A: an experimental study in rats in vivo. Gut. 2001;49:56-65 pubmed
    ..The involvement of nerves and calcium channels in the intestinal response to Clostridium difficile toxin A (luminal concentration 1 or 15 microg/ml) was studied in the small intestine of rats in vivo...
  28. Dieguez G, Fernandez N, Sanchez M, Martinez M, Garcia Villalon A, Monge L, et al. Role of nitric oxide in the cerebral circulation during hypotension after hemorrhage, ganglionic blockade and diazoxide in awake goats. Brain Res. 1999;851:133-40 pubmed
    ..These differences may be related to changes in nitric oxide release as stimuli on the endothelium (shear stress and sympathetic activity) may vary in each type of hypotension...
  29. Luzi A, Cometa M, Palmery M. Acute effects of aflatoxins on guinea pig isolated ileum. Toxicol In Vitro. 2002;16:525-9 pubmed
    ..Pretreatment with the nicotinic ganglionic blocker, hexamethonium (up to 55 microM), left AFB(1)-induced contractions unchanged. In contrast, tetrodotoxin (0...
  30. Steinbrook R. Protecting research subjects--the crisis at Johns Hopkins. N Engl J Med. 2002;346:716-20 pubmed
  31. Regan K, Jonz M, Wright P. Neuroepithelial cells and the hypoxia emersion response in the amphibious fish Kryptolebias marmoratus. J Exp Biol. 2011;214:2560-8 pubmed publisher
    ..Pre-exposure to receptor antagonists (ketanserin and hexamethonium) predictably resulted in fish emersing at a lower concentration of oxygen...
  32. Streck E, Jörres R, Huber R, Bergner A. Effects of cigarette smoke extract and nicotine on bronchial tone and acetylcholine-induced airway contraction in mouse lung slices. J Investig Allergol Clin Immunol. 2010;20:324-30 pubmed
    ..In the present study, we analyzed whether tobacco smoke has acute or chronic effects on bronchial tone and whether it alters bronchial reactivity in vitro...
  33. Mitchell A, McMahon C, Beck T, Sarazan R. Sensitivity of two noninvasive blood pressure measurement techniques compared to telemetry in cynomolgus monkeys and beagle dogs. J Pharmacol Toxicol Methods. 2010;62:54-63 pubmed publisher
    ..HDO measurements are considerably faster with a duration of approximately 8 to 15s than conventional cuff methods that can take several minutes...
  34. Havel P, Akpan J, Curry D, Stern J, Gingerich R, Ahren B. Autonomic control of pancreatic polypeptide and glucagon secretion during neuroglucopenia and hypoglycemia in mice. Am J Physiol. 1993;265:R246-54 pubmed
    ..control, respectively). These increases were abolished by hexamethonium and reduced by atropine methylnitrate (atropine)...
  35. Ishii H, Niioka T, Izumi H. Vagal visceral inputs to the nucleus of the solitary tract: involvement in a parasympathetic reflex vasodilator pathway in the rat masseter muscle. Brain Res. 2010;1312:41-53 pubmed publisher
    ..MBF increases evoked by cervical VN stimulation were reduced significantly by hexamethonium. Pretreatment with atropine reduced the MBF increase evoked by VN stimulation significantly, whereas ..
  36. Markos F, Snow H, Kidd C, Conlon K. Nitric oxide facilitates vagal control of heart rate via actions in the cardiac parasympathetic ganglia of the anaesthetised dog. Exp Physiol. 2002;87:49-52 pubmed
    ..In contrast, when the response to preganglionic stimulation had been abolished by hexamethonium (10 mg kg(-1)), the bradycardia following stimulation of postganglionic parasympathetic fibres on the atrial ..
  37. Kunz T, Scott M, Ittner L, Fischer J, Born W, Vogel J. Calcitonin gene-related peptide-evoked sustained tachycardia in calcitonin receptor-like receptor transgenic mice is mediated by sympathetic activity. Am J Physiol Heart Circ Physiol. 2007;293:H2155-60 pubmed
    ..Propranolol, in contrast to hexamethonium, blocked the CGRP-evoked increase in heart rate in both transgenic and control animals...
  38. Bian X, Heffer L, Gwynne R, Bornstein J, Bertrand P. Synaptic transmission in simple motility reflex pathways excited by distension in guinea pig distal colon. Am J Physiol Gastrointest Liver Physiol. 2004;287:G1017-27 pubmed
    ..b>Hexamethonium (nicotinic receptor antagonist, 200 microM) in the central chamber reduced IJPs evoked by far or central ..
  39. Zoccal D, Bonagamba L, Oliveira F, Antunes Rodrigues J, Machado B. Increased sympathetic activity in rats submitted to chronic intermittent hypoxia. Exp Physiol. 2007;92:79-85 pubmed
    ..0003). The injection of the ganglionic blocker hexamethonium resulted in a similar fall in MAP in CIH and control groups (-46 +/- 2 versus -41 +/- 3 mmHg)...
  40. Zidon T, Sheriff D. Diversion of blood flow from noncompliant to compliant vasculature in awake dogs: mechanical impact on right atrial pressure. Am J Physiol Heart Circ Physiol. 2006;290:H217-23 pubmed
    ..We conclude that a small (4% of cardiac output) diversion of blood flow from a noncompliant region to a compliant region reduces right atrial pressure by 0.7 mmHg...
  41. Nishida Y, Tandai Hiruma M, Kemuriyama T, Hagisawa K. Long-term blood pressure control: is there a set-point in the brain?. J Physiol Sci. 2012;62:147-61 pubmed publisher
    ..Recently, a central set-point theory has begun to be discussed. This review will discuss the mechanisms for long-term blood pressure control, based on putative biological missions of circulatory function for life support...
  42. Al Rejaie S, Dar M. Possible role of mouse cerebellar nitric oxide in the behavioral interaction between chronic intracerebellar nicotine and acute ethanol administration: observation of cross-tolerance. Neuroscience. 2006;138:575-85 pubmed
    ..Intracerebellar microinfusion of hexamethonium (1 mug once daily for 5 days): (i) did not alter ethanol-induced motor impairment indicating no tonic nicotine ..
  43. Fujimiya M, Yamamoto H, Kuwahara A. Effect of VIP and PACAP on vascular and luminal release of serotonin from isolated perfused rat duodenum. Ann N Y Acad Sci. 1998;865:495-502 pubmed
    ..These effects were not affected by the presence of atropine, hexamethonium, or TTX, suggesting that VIP, PACAP 38 and 27 exert a direct inhibitory effect on the luminal release of 5HT ..
  44. Xue B, Beltz T, Yu Y, Guo F, Gomez Sanchez C, Hay M, et al. Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension. Am J Physiol Heart Circ Physiol. 2011;300:H555-64 pubmed publisher
    ..When animals from all studies underwent ganglionic blockade with hexamethonium, there was a smaller reduction in the fall of BP in animals receiving icv AT1R or MR antagonists...
  45. Shiba K, Machida T, Uchida S, Hotta H. Effects of nicotine on regional blood flow in the olfactory bulb in rats. Eur J Pharmacol. 2006;546:148-51 pubmed
    ..artery at 10 microg increased blood flow, without changing arterial pressure; this response was abolished by hexamethonium. These results indicate that nicotine produces vasodilatation in the olfactory bulb via activation of ..
  46. Romanski K. Characteristics of phase 3-like activity and rebound excitation triggered by hexamethonium and atropine administration in the ovine small bowel. Indian J Exp Biol. 2010;48:124-32 pubmed
    Administration of hexamethonium (Hx) and atropine inhibits myoelectric and motor activity and then evokes a stimulatory effect called rebound excitation (RE) in the ovine small bowel...
  47. Rueter L, Kohlhaas K, Curzon P, Surowy C, Meyer M. Peripheral and central sites of action for A-85380 in the spinal nerve ligation model of neuropathic pain. Pain. 2003;103:269-76 pubmed
    ..Together these data further support the idea that different mechanisms underlie different pain states and suggest that the effects of NNR agonists in neuropathic pain may be due in part to peripheral actions of the compounds...
  48. Amstutz I, Diener M. Inhibition of antigen-induced muscle contractions by inhibitors of thromboxane pathway in rat small intestine. Zentralbl Veterinarmed A. 1997;44:349-59 pubmed
    ..The response to the antigen was resistant to neuronal blockers like tetrodotoxin, atropine and hexamethonium. Inhibitors of thromboxane synthesis such as the cyclooxygenase inhibitor, indomethacin, the thromboxane ..
  49. Groom C, Hawari J. Detection of hexamethonium-perchlorate association complexes using NACE-MS. Electrophoresis. 2007;28:353-9 pubmed
    Perchlorate (ClO(4) (+)) and other chlorine oxide anions were observed to complex weakly with hexamethonium (1,6-bis-(trimethylammonium)-hexane) in both aqueous and polar nonaqueous solvents...
  50. Bogeski G, Lean N, Kitchener P, Timar Peregrin A, Sanger G, Shafton A, et al. Analysis of factors that determine the compliance of rat jejunum to distension in vivo. Neurogastroenterol Motil. 2003;15:417-25 pubmed
    ..Phasic pressure increases were superimposed on the baseline pressure change. Hexamethonium blocked the phasic pressure increases, whereas the initial rapid and subsequent slower pressure decline during ..
  51. Moreira T, Takakura A, Colombari E, Menani J. Antihypertensive effects of central ablations in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1797-806 pubmed publisher
    ..The present findings suggest that in the absence of the commNTS, the AV3V region contributes to the hypertension observed in SHR by mechanisms that appear to involve enhanced angiotensinergic and sympathetic activity...
  52. Kubo T, Katsumata Y, Fukumori R, Taguchi K, Hagiwara Y. Central nicotinic receptor blockade inhibits emotionally conditioned pressor responses in rats. Experientia. 1996;52:348-52 pubmed
    ..Intracerebroventricular injection of the nicotinic receptor antagonists hexamethonium (1-10 micrograms) or pentolinium (10 micrograms) but not the muscarinic receptor antagonist methylatropine (3 ..
  53. Furukawa N, Hatano M, Fukuda H. Glutaminergic vagal afferents may mediate both retching and gastric adaptive relaxation in dogs. Auton Neurosci. 2001;93:21-30 pubmed
    ..v. administration of hexamethonium. These results suggest that adaptive relaxation in the corpus, as well as retching, may be mediated by ..