Effects of S9977 and dihydroergotamine in an animal experimental model for migraine

Cm, Villalón; Ah, Bom; Mo, Den Boer; Jp, Heiligers; Pr, Saxena

doi:10.1016/1043-6618(92)91381-p

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…infusions of the corresponding volumes of saline did not affect any haemodynamic parameter for the duration of the experiments (data not shown). The duration of action of ergotamine and DHE could not be established, as external carotid blood flow did not return to baseline values, as previously reported ( Saxena, 1974a ; Villalón et al ., 1992 ). In contrast, the duration of action of methysergide was 2.0±0.7, 7.0±1.2 and 9.0±1.9 min after 31, 100 and 310 μg min −1 , respectively.…”

Section: Resultsmentioning

confidence: 61%

“…Thus, these findings suggest that such responses were caused by a selective constriction in the external carotid vascular bed. Notwithstanding, unlike methysergide, the responses to ergotamine and DHE were of long duration, as previously observed in vivo ( Saxena, 1974a ; Den Boer et al ., 1991a ; Villalón et al ., 1992 ; De Vries et al ., 1998b ) and in vitro ( Müller‐Schweinitzer & Weidmann, 1978 ; MaassenVanDenBrink et al ., 1998 ). Although there is no clear‐cut explanation for this difference, it has been suggested, albeit not categorically proven, that it may be due to a slow dissociation from its receptors or a sequestration and subsequent diffusion out of a local nonsaturable compartment ( Müller‐Schweinitzer & Weidmann, 1978 ; Martin et al ., 1995 ).…”

Section: Discussionmentioning

confidence: 99%

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Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT_1B/1D receptors and α₂‐adrenoceptors

Villalón

Vries

Rabelo

et al. 1999

British J Pharmacology

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1 The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DHE) produce selective vasoconstriction in the external carotid bed of vagosympathectomized dogs anaesthetized with pentobarbital and arti®cially respired, but the receptors involved have not yet been completely characterized. Since the above drugs display anity for several binding sites, including aadrenoceptors and several 5-HT 1 and 5-HT 2 receptor subtypes, this study has analysed the mechanisms involved in the above responses. 2 Intracarotid (i.c.) infusions during 1 min of methysergide (31 ± 310 mg min 71 ), ergotamine (0.56 ± 5.6 mg min 71 ) or DHE (5.6 ± 31 mg min 71 ) dose-dependently reduced external carotid blood¯ow (ECBF) by up to 46+4, 37+4 and 49+5%, respectively. Blood pressure and heart rate remained unchanged. 3 The reductions in ECBF by methysergide were abolished and even reversed to increases in animals pre-treated with GR127935 (10 mg kg 71 , i.v.). 4 The reductions in ECBF by ergotamine and DHE remained unchanged in animals pre-treated (i.v.) with prazosin (300 mg kg 71), but were partly antagonized in animals pre-treated with either GR127935 (10 or 30 mg kg 71 ) or yohimbine (1000 mg kg 71 ). Pre-treatment with a combination of GR127935 (30 mg kg 71 ) and yohimbine (1000 mg kg 71 ) abolished the responses to both ergotamine and DHE. The above doses of antagonists were shown to produce selective antagonism at their respective receptors. 5 These results suggest that the external carotid vasoconstrictor responses to methysergide primarily involve 5-HT 1B/1D receptors, whereas those to ergotamine and DHE are mediated by 5-HT 1B/1D receptors as well as a 2 -adrenoceptors.

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Section: Resultsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT_1B/1D receptors and α₂‐adrenoceptors

Villalón

Vries

Rabelo

et al. 1999

British J Pharmacology

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“…Anti-HIV-1 inhibitor (Wan et al, 2012) LOPAC library from Sigma Dihydroergotamine methanesulfonate Antimigraine characteristics (Villalon et al, 1992) The compounds selected from virtual screening and biophysical studies have demonstrated potential against SARS-CoV-2 RdRp complex. Specifically, out of the compounds tested,…”

Section: Fangchinolinementioning

confidence: 99%

“…It is worth noting that these three compounds are utilized in various medications. Dihydroergotamine methanesulfonate, for instance, is employed as an antimigraine agent (Villalon et al, 1992), while chikusetsusaponin iva is known for its antiviral, anti-inflammatory, and antithrombotic properties (Dahmer et al, 2012;Rattanathongkom et al, 2009;Xu et al, 2021). Additionally, rapamycin serves as an immunosuppressive and antitumor agent (Houchens et al, 1983;Malagelada et al, 2010).…”

Section: Fangchinolinementioning

confidence: 99%

Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2

Rani

Nehul

Choudhary

et al. 2023

Preprint

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SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex consisting of nsp12, nsp7, and nsp8 as the key enzyme for viral genome replication and is a proven antiviral drug target. In this study, molecular interactions of nsp7 and nsp8 with nsp12 and the active site of nsp12 were coterminously targeted using in-silico screening of small molecule libraries to identify potential antivirals. Surface plasmon resonance (SPR) based assay using purified nsp7 and nsp8 proteins was developed, and the binding of identified molecules to targets was validated. The antiviral efficacy of identified small molecules was evaluated using cell-based assays, and potent antiviral effect with EC50 values of 0.56 uM, 0.73 uM, and 2.8 uM was demonstrated by fangchinoline, cepharanthine, and sennoside B, respectively. Further in vivo, investigation using hACE2 mice is being conducted. This is the first study that targets multiple sites in the RdRp complex of SARS-CoV-2 using a structure-based molecular repurposing approach and suggests potential therapeutic options for emerging variants of SARS-CoV-2.

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“…This reflects, in part, species variations which have been addressed in a recent reclassification (Hartig et al, 1996) and the possibility that there is as yet an undiscovered receptor. The paradox remains that, whereas the vasoconstrictor effect of sumatriptan is blocked by methiothepin (Hamel and Bouchard, 1991), a potent but not specific 5HT 1B/D antagonist (Peroutka and McCarthy, 1989;Schoeffter and Hoyer, 1989), the response is not antagonized by metergoline either in vivo (Perren et al, 1991;Villalon et al, 1992) or in vitro (Bax et al, 1992), although metergoline is more potent than methiothepin at the 5HT 1D receptor (Schoeffter et al, 1988;Waeber et al, 1988). These data may simply be an amalgam of species variations and varying antagonist potencies of metergoline and methiothepin, although the intriguing possibility remains that a further 5HTl-like receptor is yet to be discovered.…”

Section: Mechanical Stimulationmentioning

confidence: 99%

Sumatriptan can inhibit trigeminal afferents by an exclusively neural mechanism

Hoskin

Kaube

Goadsby

1996

Brain

107

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Mechanical distortion of the human cranial venous sinuses is painful as is cranial venous sinus distension during migraine. Sumatriptan, the serotonin (5HT)IB/D-like receptor agonist, is highly effective in relieving migraine headache and part of its action may be due to constriction of cranial dural blood vessels. Using immunohistochemical detection of the immediate early gene Fos, we have mapped the spatial pattern of neural activation in the caudal medulla and the upper cervical spinal cord (C1, C2 and C3) in cats following either electrical or mechanical stimulation of the superior sagittal sinus. Fourteen cats were anaesthetized with alpha-chloralose and prepared for physiological monitoring of blood pressure, heart rate, rectal temperature and expired CO2. Electrical stimulation evoked significant increases in the (median) numbers of Fos-positive cells in laminae I and IIo of the superficial dorsal horn of C1, C2 and C3 cervical spinal cord (88, 92 and 18 cells, respectively) and of the trigeminal nucleus caudalis (TNC) (81 cells). Mechanical stimulation revealed a similar pattern of neural activation but with reduced intensity in laminae I and IIo of the TNC (38 cells) and of C1 and C2 (32 and 31 cells, respectively). The temporalis muscle was stimulated mechanically in the control group and the numbers and distribution of Fos-positive cells were no different from those in non-stimulated controls. Treatment with sumatriptan reduced the numbers of Fos-positive cells found in laminae I and IIo of the TNC and C2 (6, 13 cells and 9 cells, respectively) after mechanical stimulation. These data suggest that the neural effect of sumatriptan alone is sufficient for significant attenuation of transmission in the trigeminal system. The fact that sumatriptan can inhibit trigeminal activation without its vascular effects suggests that drugs without a significant activity on blood vessels may be effective in the treatment of migraine.

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Effects of S9977 and dihydroergotamine in an animal experimental model for migraine

Cited by 11 publications

References 28 publications

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT_1B/1D receptors and α₂‐adrenoceptors

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT_1B/1D receptors and α₂‐adrenoceptors

Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2

Sumatriptan can inhibit trigeminal afferents by an exclusively neural mechanism

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Effects of S9977 and dihydroergotamine in an animal experimental model for migraine

Cited by 11 publications

References 28 publications

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT1B/1D receptors and α2‐adrenoceptors

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT1B/1D receptors and α2‐adrenoceptors

Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2

Sumatriptan can inhibit trigeminal afferents by an exclusively neural mechanism

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Product

Resources

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Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT_1B/1D receptors and α₂‐adrenoceptors

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5‐HT_1B/1D receptors and α₂‐adrenoceptors