Summary: An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.

Top Publications

  1. Radhakrishnan R, King E, Dickman J, Herold C, Johnston N, Spurgin M, et al. Spinal 5-HT(2) and 5-HT(3) receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats. Pain. 2003;105:205-13 pubmed
    ..The (1). alpha(2)-adrenergic antagonist yohimbine (30 microg), (2). 5-HT antagonist methysergide (5-HT(1). and 5-HT(2). 30 microg), one of the 5-HT receptor subtype antagonists, (3)...
  2. Peres e Serra A, Ashmawi H. Influence of naloxone and methysergide on the analgesic effects of low-level laser in an experimental pain model. Rev Bras Anestesiol. 2010;60:302-10 pubmed publisher
    ..were separated into five groups: Carrageenin; Laser (LPT); Non-coherent light; LPT + Naloxone; and LPT + Methysergide. Low-Level Laser phototherapy proved to be an effective analgesic method, while non-coherent light did not show ..
  3. Hardy A, Palouzier Paulignan B, Duchamp A, Royet J, Duchamp Viret P. 5-Hydroxytryptamine action in the rat olfactory bulb: in vitro electrophysiological patch-clamp recordings of juxtaglomerular and mitral cells. Neuroscience. 2005;131:717-31 pubmed
    ..This is expected to enrich the understanding of its determining role in olfactory learning. ..
  4. Dacks A, Green D, Root C, Nighorn A, Wang J. Serotonin modulates olfactory processing in the antennal lobe of Drosophila. J Neurogenet. 2009;23:366-77 pubmed publisher
    ..Our data suggest that the complexity of serotonin modulation in the antennal lobe accommodates coding stability in a glomerular pattern and flexible projection neuron sensitivity under different physiological conditions. ..
  5. Lima C, Souza V, Soares A, Macedo M, Tavares de Lima W, Vargaftig B. Interference of methysergide, a specific 5-hydroxytryptamine receptor antagonist, with airway chronic allergic inflammation and remodelling in a murine model of asthma. Clin Exp Allergy. 2007;37:723-34 pubmed
    ..Two hours before each challenge, they were treated with methysergide (intranasally, 40 microg/kg)...
  6. Pradalier A, Baudesson G, Vincent D, Imberty Campinos C. [Treatment of cluster headache]. Rev Med Interne. 2001;22:151-62 pubmed
    ..the drugs limit the choice of the prophylactic treatment: corticosteroids in a tapering course, verapamil and methysergide are the most useful treatments of the episodic form...
  7. Fox D, Handberg G, Hartley M, Monagle J, Pennefather J. Actions of some autacoids and peptides, including relaxin, on costo-uterine muscle from rats. Clin Exp Pharmacol Physiol. 1989;16:561-9 pubmed
    ..The effects of serotonin were reduced, but not reversed, by methysergide (0.94 mumol/L). 4...
  8. Telegdy G, Kokavszky K. The action of pituitary adenylate cyclase activating polypeptide (PACAP) on passive avoidance learning. The role of transmitters. Brain Res. 2000;874:194-9 pubmed
    ..blockers attenuated the action of PACAP on this consolidation: haloperidol, phenoxybenzamine, propranolol and methysergide. An antagonist of PACAP 38, PACAP 6-38, and also nitro-L-arginine (the latter blocks the enzyme nitric oxide ..
  9. Telegdy G, Tiricz H, Adamik A. Involvement of neurotransmitters in urocortin-induced passive avoidance learning in mice. Brain Res Bull. 2005;67:242-7 pubmed
    ..on consolidation: haloperidol, atropine, phenoxybenzamine, bicuculline, the CRF antagonist CRF9-41 and methysergide. Propranolol attenuated, but did not fully block the action of urocortin, while naloxone and nitro-L-arginine ..

More Information


  1. ST JOHN W, Leiter J. Discharge of the hypoglossal nerve cannot distinguish eupnea from gasping, as defined by phrenic discharge, in the in situ mouse. J Appl Physiol (1985). 2009;107:686-95 pubmed publisher
    ..2 ms) were the same. The uncoupling of hypoglossal from phrenic discharge in eupnea was exacerbated by methysergide, an antagonist of serotonin receptors...
  2. Hendrix S. Nonestrogen management of menopausal symptoms. Endocrinol Metab Clin North Am. 1997;26:379-90 pubmed
    ..This article reviews treatment alternatives to estrogen replacement therapy for symptomatic relief. ..
  3. Koshizaki M, Kawamata M, Shimada S, Saito Y, Collins J. 5-HT3 receptors partially mediate halothane depression of spinal dorsal horn sensory neurons. Anesth Analg. 2003;96:1027-31, table of contents pubmed
    ..In the presence of halothane, methysergide, a nonselective 5-HT antagonist, and tropisetron, a selective 5-HT(3) antagonist, significantly reversed the ..
  4. Ohta Y, Kobayashi T, Ishiguro I. Role of endogenous serotonin and histamine in the pathogenesis of gastric mucosal lesions in unanaesthetised rats with a single treatment of compound 48/80, a mast cell degranulator. Pharmacol Res. 1999;39:261-7 pubmed
    ..Pretreatment with either cyproheptadine (a serotonin and histamine antagonist) or methysergide (a serotonin antagonist) prevented the formation of gastric mucosal lesions with attenuation of reduced gastric ..
  5. Mulleners W, Whitmarsh T, Steiner T. Noncompliance may render migraine prophylaxis useless, but once-daily regimens are better. Cephalalgia. 1998;18:52-6 pubmed
    ..We conclude that routine use of drug prophylaxis in migraine may be so seriously undermined by poor compliance that it has little chance of efficacy. Returned-pill counting is inadequate for compliance assessment. ..
  6. Bhattacharyya S, Schapira A, Mikhailidis D, Davar J. Drug-induced fibrotic valvular heart disease. Lancet. 2009;374:577-85 pubmed publisher
    ..between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s...
  7. Tfelt Hansen P, Jansen I, Edvinsson L. Methylergometrine antagonizes 5 HT in the temporal artery. Eur J Clin Pharmacol. 1987;33:77-9 pubmed
    Methylergometrine, the main metabolite of methysergide, has 40-times greater 5 HT antagonistic potency than methysergide in isolated segments of human temporal artery...
  8. De Sarro G, De Sarro A. Antagonists of adenosine and alpha-2-adrenoceptors reverse the anticonvulsant effects of tizanidine in DBA/2 mice. Neuropharmacology. 1989;28:211-5 pubmed
    ..p.), yohimbine (1 mg/kg i.p.) or piperoxan (20 mg/kg i.p.). Methysergide, a serotonin antagonists, did not significantly reduce the anticonvulsant effects of tizanidine...
  9. Abelli L, Somma V, Maggi C, Regoli D, Astolfi M, Parlani M, et al. Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors. J Auton Pharmacol. 1989;9:253-63 pubmed
    ..71 nmol kg-1 i.v.) was unaffected by pretreatment with antihistaminic drugs or methysergide. 3...
  10. Galer B, Lipton R, Solomon S, Newman L, Spierings E. Myocardial ischemia related to ergot alkaloids: a case report and literature review. Headache. 1991;31:446-50 pubmed
    Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconstrictive properties...
  11. De Swert K, Lefebvre R, Pauwels R, Joos G. Role of the tachykinin NK(1) receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea. Pulm Pharmacol Ther. 2007;20:588-95 pubmed
    ..Responses to ovalbumin were abrogated by methysergide, a broad 5-hydroxytryptamine receptor antagonist...
  12. Mitchell G, Turner D, Henderson D, Foley K. Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008;161:230-8 pubmed publisher
    ..made before and after spinal or intravenous administration of a broad-spectrum serotonin receptor antagonist (methysergide, 1-2mg total) and a selective 5-HT2-receptor antagonist (ketanserin, 5-12 mg total)...
  13. Burrell B, Sahley C. Serotonin mediates learning-induced potentiation of excitability. J Neurophysiol. 2005;94:4002-10 pubmed
    ..Potentiation of S-cell excitability by 5-HT was blocked by the 5-HT receptor antagonist methysergide and by intracellular injection of the G-protein inhibitor GDP-beta-S, indicating that a metabotropic 5-HT ..
  14. Koizuka S, Obata H, Sasaki M, Saito S, Goto F. Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats. Can J Anaesth. 2005;52:498-505 pubmed
    ..We examined the effects of intrathecal pretreatment with yohimbine, an alpha2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine...
  15. Andrade Franzé G, Andrade C, De Luca L, de Paula P, Menani J. Lateral parabrachial nucleus and central amygdala in the control of sodium intake. Neuroscience. 2010;165:633-41 pubmed publisher the blockade of serotonergic mechanisms or activation of alpha(2)-adrenoceptors with bilateral injections of methysergide or moxonidine, respectively, into the LPBN...
  16. Choi S, Han K, Lee J, Lee H, Han E, Kim D, et al. Antinociceptive mechanisms of orally administered decursinol in the mouse. Life Sci. 2003;73:471-85 pubmed
    ..Intraperitoneal (i.p.) pretreatment with yohimbine, methysergide, cyproheptadine, ranitidine, or 3,7-dimethyl-1-propargylxanthine (DMPX) attenuated inhibition of the tail-flick ..
  17. Lee Y, Lin C, Jiang H, Depaul M, Lin V, Silver J. Nerve regeneration restores supraspinal control of bladder function after complete spinal cord injury. J Neurosci. 2013;33:10591-606 pubmed publisher
    ..Our studies provide evidence that an enhanced nerve grafting strategy represents a potential regenerative treatment after severe spinal cord injury. ..
  18. Hanyu N, Dodds W, layman R, Hogan W. Cholecystokinin-induced contraction of opossum sphincter of Oddi. Mechanism of action. Dig Dis Sci. 1990;35:567-76 pubmed
    ..Such increases were antagonized substantially by hexamethonium, atropine, or methysergide. The CCK antagonist, L364718, antagonized the excitatory SO response to CCK-OP infusion or intraduodenal ..
  19. Kremer E, Lev Tov A. GABA-receptor-independent dorsal root afferents depolarization in the neonatal rat spinal cord. J Neurophysiol. 1998;79:2581-92 pubmed
    ..Possible implications of potassium transients in the developing and the adult mammalian spinal cord are discussed. ..
  20. Cayetanot F, Bodineau L, Frugière A. 5-HT acting on 5-HT(1/2) receptors does not participate in the in vitro hypoxic respiratory depression. Neurosci Res. 2001;41:71-8 pubmed
    ..5-HT (30 microM) superfusion elicited a rapid increase in respiratory frequency, prevented by a treatment with methysergide (a 5-HT(1/2) receptor antagonist) (40 microM)...
  21. Kahn R, Kalus O, Wetzler S, Cahn W, Asnis G, van Praag H. Effects of serotonin antagonists on m-chlorophenylpiperazine-mediated responses in normal subjects. Psychiatry Res. 1990;33:189-98 pubmed
    ..To address MCPP's selectivity for 5HT, this study tested whether two different 5HT antagonists, methysergide (4 mg p.o.) and metergoline (4 mg p.o.), could block the hormonal and behavioral effects of MCPP (0.5 mg/kg p.o...
  22. Oliveira Margatho L, Pereira Barbosa S, Antonio De Luca L, Vanderlei Menani J. Central serotonergic and adrenergic/imidazoline inhibitory mechanisms on sodium and water intake. Brain Res. 2002;956:103-9 pubmed
    ..2+/-1.0 ml/2 h) and NaCl intake (0.7+/-0.2 ml/2 h). Bilateral injections of methysergide (4 microg/0.2 microl each site) into the LPBN increased 0.3 M NaCl intake (6.4+/-1.9 ml/2 h), not water intake...
  23. Newman Tancredi A, Conte C, Chaput C, Verriele L, Audinot Bouchez V, Lochon S, et al. Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy. Naunyn Schmiedebergs Arch Pharmacol. 1997;355:682-8 pubmed
    ..Of the prophylactic antimigraine drugs tested, methysergide and lisuride behaved as efficacious agonists (Emax > or = 90% relative to 5-HT) whereas pitozifen and (-)..
  24. Silveira J, Dias Q, Del Bel E, Prado W. Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats. Mol Pain. 2010;6:17 pubmed publisher
    ..contralateral lamina V of atropine-treated rats; were inhibited in the ipsilateral lamina I/II by 5-HT1/2B/2C (methysergide), 5-HT2A (ketanserin) or 5-HT1/2A/2C/5/6/7 (methiothepin) receptors antagonists, in the ipsilateral lamina V by ..
  25. Matsuda M, Imaoka T, Vomachka A, Gudelsky G, Hou Z, Mistry M, et al. Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev Cell. 2004;6:193-203 pubmed
    ..Thus, autocrine-paracrine serotonin signaling is an important regulator of mammary homeostasis and early involution. ..
  26. Saeed S, Rasheed H, Gilani A. Synergism interaction between arachidonic acid by 5-hydroxytryptamine in human platelet aggregation is mediated through multiple signalling pathways. Acta Pharmacol Sin. 2003;24:958-64 pubmed
    ..2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC(50)=5.2 nmol/L; cyproheptadine IC(50)=0...
  27. Peatfield R. Headache currents commentary. Headache. 2012;52:715 pubmed publisher
    ..The clinical aspects of 3 of the oldest headache medicines (ergotamine tartrate, dihydroergotamine, and methysergide) will be discussed here...
  28. Erdinler I, Afsar N, Sanli A, Okmen E. Asystole associated with cluster headache. Can J Cardiol. 2004;20:1369-70 pubmed
    ..The asystole and syncope attacks disappeared completely following prophylactic therapy with methysergide maleate...
  29. Herbert M, Weis R, Holzer P, Roewer N. Peristalsis in the Guinea pig small intestine in vitro is impaired by acetaminophen but not aspirin and dipyrone. Anesth Analg. 2005;100:120-7 pubmed
    ..but not changed by L-nitro-arginine methylester (L-NAME), its inactive enantiomer D-NAME, acetylsalicylic acid, methysergide, or tropisetron. Acetylsalicylic acid and dipyrone did not affect peristalsis...
  30. Sevcik J, Petrovicky P, Ruzicka V, Slansky J, Masek K. Structures and pathways of the central nervous system are potentially involved in the serotonergic modulation of gastrointestinal activity. Methods Find Exp Clin Pharmacol. 2002;24:669-73 pubmed
  31. May A, Leone M, Afra J, Linde M, Sandor P, Evers S, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol. 2006;13:1066-77 pubmed
    ..v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments...
  32. Hammond D, Nelson V, Thomas D. Intrathecal methysergide antagonizes the antinociception, but not the hyperalgesia produced by microinjection of baclofen in the ventromedial medulla of the rat. Neurosci Lett. 1998;244:93-6 pubmed
    ..pathways in the biphasic effects of baclofen, rats were pretreated intrathecally with either 30 microg of methysergide or saline. Ten minutes later, either saline, 0...
  33. Hannon J, Tigani B, Williams I, Mazzoni L, Fozard J. Mechanism of airway hyperresponsiveness to adenosine induced by allergen challenge in actively sensitized Brown Norway rats. Br J Pharmacol. 2001;132:1509-23 pubmed
    ..v. injection of capsaicin. It was, however, blocked selectively by disodium cromoglycate methysergide or ketanserin and reduced in animals treated sub-chronically with compound 48/80. 4...
  34. Waldron J, Reid A, Sawynok J. Amitriptyline produces multiple influences on the peripheral enhancement of nociception by P2X receptors. Eur J Pharmacol. 2004;499:275-83 pubmed
    ..resulting from inhibition of uptake, as phentolamine (alpha(1)/alpha(2)-adrenergic receptor antagonist) and methysergide (5-hydroxytryptamine or 5-HT(1)/5-HT(2) receptor antagonist) inhibit the augmented flinching produced by ..
  35. Gore A, Terasawa E. Neural circuits regulating pulsatile luteinizing hormone release in the female guinea-pig: opioid, adrenergic and serotonergic interactions. J Neuroendocrinol. 2001;13:239-48 pubmed
  36. Miura T, Okazaki R, Yoshida H, Namba H, Okai H, Kawamura M. Mechanisms of analgesic action of neurotropin on chronic pain in adjuvant-induced arthritic rat: roles of descending noradrenergic and serotonergic systems. J Pharmacol Sci. 2005;97:429-36 pubmed
    ..antagonist MDL72222 (30 nmol/animal), and slightly inhibited by the non-selective serotonin receptor antagonist methysergide (100 nmol/animal)...
  37. Kawamata T, Omote K, Sonoda H, Kawamata M, Namiki A. Analgesic mechanisms of ketamine in the presence and absence of peripheral inflammation. Anesthesiology. 2000;93:520-8 pubmed
    ..In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine...
  38. Walker E, Foley J. Acquisition session length modulates consolidation effects produced by 5-HT2C ligands in a mouse autoshaping-operant procedure. Behav Pharmacol. 2010;21:83-9 pubmed publisher
    ..full agonist), m-chlorophenylpiperazine (partial agonist), mianserin, and SB206 553 (inverse agonists), and methysergide and (+)-2-bromo lysergic acid diethylamide (+)-hydrogen tartrate (neutral antagonists)...
  39. Bergmans M, Merkus J, Corbey R, Schellekens L, Ubachs J. Effect of Bellergal Retard on climacteric complaints: a double-blind, placebo-controlled study. Maturitas. 1987;9:227-34 pubmed
    ..It was concluded that studies on medication for climacteric complaints should not only be placebo-controlled, but also be of at least 8 to 12 wk duration for proper evaluation. ..
  40. Castilho V, Macedo C, Brandao M. Role of benzodiazepine and serotonergic mechanisms in conditioned freezing and antinociception using electrical stimulation of the dorsal periaqueductal gray as unconditioned stimulus in rats. Psychopharmacology (Berl). 2002;165:77-85 pubmed
    ..Further studies with other opioid and 5-HT(2) receptor antagonists are still needed to confirm the conclusions drawn from the present work. ..
  41. Centurión D, Mehotra S, Sánchez López A, Gupta S, Maassenvandenbrink A, Villalón C. Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat. Eur J Pharmacol. 2006;535:234-42 pubmed
    ..These ligands included: methiothepin, methysergide and metergoline (5-HT(1)/5-HT2); WAY-100635, buspirone, ipsapirone and 8-hydroxy-2-(di-n-propylamino)tetralin (..
  42. Lavich T, Cordeiro R, Calixto J, E Silva P, Martins M. Combined action of vasoactive amines and bradykinin mediates allergen-evoked thermal hyperalgesia in rats. Eur J Pharmacol. 2003;462:185-92 pubmed
    ..Allergen-evoked hyperalgesia was inhibited by intraperitoneal treatment with meclizine or methysergide, histamine and 5-hydroxytryptamine receptor antagonists...
  43. Holm L, Jägare A. Influence of tactile stimulation of the rat gastric mucosa on blood flow and acid output. Am J Physiol. 1993;265:G303-9 pubmed
    ..Pretreatment with lidocaine, methysergide, or hexamethonium did not change the results of tactile stimulation on the blood flow...
  44. Jovanovic Micic D, Samardzic R, Beleslin D. The role of alpha-adrenergic mechanisms within the area postrema in dopamine-induced emesis. Eur J Pharmacol. 1995;272:21-30 pubmed
    ..blocking agent (mecamylamine), an opioid receptor antagonist (naloxone) and a 5-HT receptor antagonist (methysergide), all injected intracerebroventricularly, had no significant effect on emesis evoked by intracerebroventricular ..
  45. Amelin A, Ivanov V, Ignatov I, Tumelevich B, Pushkarev A, Usachev N. [The effect of tropoxin on the neurogenic and vasogenic inflammation of the dura mater vessels]. Eksp Klin Farmakol. 1999;62:14-7 pubmed
    ..It is suggested that the mechanism of the tropoxin antimigraine effect is realized through the presynaptic 5-HT1 receptors of afferent endings of the trigeminal nerve and the postsynaptic 5-HT2B/2C receptors of the dura mater vessels...
  46. Lambert G, Shimomura T, Boers P, Gordon V, Donaldson C, Zagami A. Serotonin infusions inhibit sensory input from the dural vasculature. Cephalalgia. 1999;19:639-50 pubmed
    ..Inhibition was suppressed by prior intravenous injection of the 5HT antagonists methysergide (1 mg/kg) and methiothepin (1 mg/kg)...
  47. Fribourg M, Moreno J, Holloway T, Provasi D, Baki L, Mahajan R, et al. Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell. 2011;147:1011-23 pubmed publisher
    ..The closely related non-antipsychotic drugs, such as ritanserin and methysergide, also block 2AR function, but they lack comparable neuropsychological effects...
  48. Hayashi K, Sato H, Kaise T, Ohmori K, Ishii A, Sano J, et al. Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats. Eur J Pharmacol. 2001;425:219-27 pubmed
    ..Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage...
  49. Goadsby P, Cohen A. [Pathophysiology and treatment of trigeminal autonomic cephalalgias]. Schmerz. 2008;22 Suppl 1:7-10 pubmed publisher
    ..It is important to recognize and differentiate between these syndromes because they react very well, but very selectively to therapy. ..
  50. Janvier J, Peyraud Waitzenegger M, Soulier P. Effects of serotonin on the cardio-circulatory system of the European eel (Anguilla anguilla) in vivo. J Comp Physiol B. 1996;166:131-7 pubmed
    ..The effects of serotonin on cardiac parameters were suppressed either by methysergide or a bilateral section of the cardiac vagus...
  51. Heinze A, Heinze Kuhn K, Gobel H. [Preventive medication in migraine headache : Individualized clinical pathways]. Schmerz. 2010;24:73-9; quiz 80 pubmed publisher
    ..The treatment algorithm presented here tries to bridge the gulf between general treatment guidelines and the actual needs of the patient. From this, feasible clinical pathways are derived for individualized treatment. ..
  52. Guimarães A, Cruz Höfling M, Ferreira de Araújo P, Bon C, Lôbo de Araújo A. Pharmacological and histopathological characterization of Bothrops lanceolatus (Fer de lance) venom-induced edema. Inflamm Res. 2004;53:284-91 pubmed
    ..Dexamethasone (1 mg/kg, s.c.), methysergide (6 mg/kg, i.p.), HOE 140 (0.6 mg/kg, i.v.) and mepyramine (6 mg/kg, i.p.) significantly ( p < 0...