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Carlos M. Villalón - One of the best experts on this subject based on the ideXlab platform.
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activation of 5 hydroxytryptamine1b 1d 1f receptors as a mechanism of action of Antimigraine Drugs
Expert Opinion on Pharmacotherapy, 2013Co-Authors: Martha Ramirez B Rosas, Carlos M. Villalón, Sieneke Labruijere, Antoinette Maassen VandenbrinkAbstract:Introduction: The introduction of the triptans (5-hydroxytryptamine (5-HT)1B/1D receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine. Areas covered: In this review the different types of Antimigraine Drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific Antimigraine Drugs were the ergot alkaloids, consisting of ergotamine, dihydroergotamine and methysergide, which are agonists at 5-HT receptors, but can also bind α-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT1B/1D receptor agonists, showing fewer side effects due to their receptor specificity. In the last years, compounds that bind specifically to 5-HT1D, 5-HT1F and 5-HT7 receptors have been explored for their Antimigraine potential. Furthermore, the serotonergic system seems to act in tight connection ...
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Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of Antimigraine Drugs.
Expert Opinion on Pharmacotherapy, 2013Co-Authors: Martha B. Ramírez Rosas, Carlos M. Villalón, Sieneke Labruijere, Antoinette Maassen VandenbrinkAbstract:Introduction: The introduction of the triptans (5-hydroxytryptamine (5-HT)1B/1D receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine. Areas covered: In this review the different types of Antimigraine Drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific Antimigraine Drugs were the ergot alkaloids, consisting of ergotamine, dihydroergotamine and methysergide, which are agonists at 5-HT receptors, but can also bind α-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT1B/1D receptor agonists, showing fewer side effects due to their receptor specificity. In the last years, compounds that bind specifically to 5-HT1D, 5-HT1F and 5-HT7 receptors have been explored for their Antimigraine potential. Furthermore, the serotonergic system seems to act in tight connection ...
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role of 5 ht1b 1d receptors in the reduction of formalin induced nociception and secondary allodynia hyperalgesia produced by Antimigraine Drugs in rats
Life Sciences, 2013Co-Authors: Beatriz Godinezchaparro, Francisco J Lopezsantillan, Carlos F Arguelles, Carlos M. Villalón, Vinicio GranadossotoAbstract:Abstract Aims The present study analyzed the potential antinociceptive effect of the Antimigraine Drugs sumatriptan, dihydroergotamine or methysergide in rats submitted to the formalin test. Moreover, by using selective antagonists, the role of 5-HT 1B/1D serotonergic receptors was investigated in the antinociception induced by these Antimigraine Drugs. Main methods The formalin test was used to assess the nociceptive activity. Overt pain-like behavior (flinching, 1 h) and evoked nociception (long-lasting secondary mechanical allodynia and hyperalgesia, 6 days) were determined in the same rat. Key findings Ipsilateral, but not contralateral, pre-treatment (in μg/paw) with sumatriptan (10–300), methysergide (1–30) or dihydroergotamine (1–30) significantly prevented flinching behavior (at 1 h) as well as secondary allodynia and hyperalgesia (at day 6) induced by formalin. Interestingly, the antinociceptive (flinching), antiallodynic and antihyperalgesic effects of sumatriptan were completely prevented by peripheral pre-treatment with selective antagonists at the 5-HT 1B (SB 224289; 100) or 5-HT 1D (BRL 15572; 100) receptors. In contrast, the acute antinociceptive effects of methysergide and dihydroergotamine were partially prevented by SB 224289 and BRL 15572. The antiallodynic and antihyperalgesic effects of both Drugs were completely prevented by BRL 15572 and partially prevented by SB 224289. Given alone, SB 224289 or BRL 15572 did not modify per se the long-lasting secondary allodynia and hyperalgesia. Significance The above findings suggest that: (i) the Antimigraine Drugs sumatriptan, methysergide and dihydroergotamine reduce the acute and chronic nociception induced by formalin; and (ii) this antinociceptive effect results from activation of peripheral 5-HT 1B/1D serotonergic receptors.
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Role of 5-HT1B/1D receptors in the reduction of formalin-induced nociception and secondary allodynia/hyperalgesia produced by Antimigraine Drugs in rats
Life Sciences, 2013Co-Authors: Beatriz Godínez-chaparro, Carlos F Arguelles, Francisco J. López-santillán, Carlos M. Villalón, Vinicio Granados-sotoAbstract:Abstract Aims The present study analyzed the potential antinociceptive effect of the Antimigraine Drugs sumatriptan, dihydroergotamine or methysergide in rats submitted to the formalin test. Moreover, by using selective antagonists, the role of 5-HT 1B/1D serotonergic receptors was investigated in the antinociception induced by these Antimigraine Drugs. Main methods The formalin test was used to assess the nociceptive activity. Overt pain-like behavior (flinching, 1 h) and evoked nociception (long-lasting secondary mechanical allodynia and hyperalgesia, 6 days) were determined in the same rat. Key findings Ipsilateral, but not contralateral, pre-treatment (in μg/paw) with sumatriptan (10–300), methysergide (1–30) or dihydroergotamine (1–30) significantly prevented flinching behavior (at 1 h) as well as secondary allodynia and hyperalgesia (at day 6) induced by formalin. Interestingly, the antinociceptive (flinching), antiallodynic and antihyperalgesic effects of sumatriptan were completely prevented by peripheral pre-treatment with selective antagonists at the 5-HT 1B (SB 224289; 100) or 5-HT 1D (BRL 15572; 100) receptors. In contrast, the acute antinociceptive effects of methysergide and dihydroergotamine were partially prevented by SB 224289 and BRL 15572. The antiallodynic and antihyperalgesic effects of both Drugs were completely prevented by BRL 15572 and partially prevented by SB 224289. Given alone, SB 224289 or BRL 15572 did not modify per se the long-lasting secondary allodynia and hyperalgesia. Significance The above findings suggest that: (i) the Antimigraine Drugs sumatriptan, methysergide and dihydroergotamine reduce the acute and chronic nociception induced by formalin; and (ii) this antinociceptive effect results from activation of peripheral 5-HT 1B/1D serotonergic receptors.
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potential mechanisms of prospective Antimigraine Drugs a focus on vascular side effects
Pharmacology & Therapeutics, 2011Co-Authors: Kayi Y Chan, Steve Vermeersch, Jan De Hoon, Carlos M. Villalón, Antoinette MaassenvandenbrinkAbstract:Abstract Currently available Drugs for the acute treatment of migraine, i.e. ergot alkaloids and triptans, are cranial vasoconstrictors. Although cranial vasoconstriction is likely to mediate—at least a part of—their therapeutic effects, this property also causes vascular side-effects. Indeed, the ergot alkaloids and the triptans have been reported to induce myocardial ischemia and stroke, albeit in extremely rare cases, and are contraindicated in patients with known cardiovascular risk factors. In view of these limitations, novel Antimigraine Drugs devoid of vascular (side) effects are being explored. Currently, calcitonin gene-related peptide (CGRP) receptor antagonists, which do not have direct vasoconstrictor effects, are under clinical development. Other classes of Drugs, such as 5-HT 1F receptor agonists, glutamate receptor antagonists, nitric oxide synthase inhibitors, VPAC/PAC receptor antagonists and gap junction modulators, have also been proposed as potential targets for acute Antimigraine Drugs. Although these prospective Drugs do not directly induce vasoconstriction, they may well induce indirect vascular effects by inhibiting or otherwise modulating the responses to endogenous vasoactive substances. These indirect vascular effects might contribute to the therapeutic efficacy of the previously mentioned compounds, but may alternatively also lead to vascular side-effects. As described in the current review, some of the prospective Antimigraine Drugs with a proposed non-vascular mechanism of action may still have direct or indirect vascular effects.
Antoinette Maassenvandenbrink - One of the best experts on this subject based on the ideXlab platform.
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the need for new acutely acting Antimigraine Drugs moving safely outside acute medication overuse
Journal of Headache and Pain, 2019Co-Authors: Willem Sebastiaan Van Hoogstraten, Antoinette MaassenvandenbrinkAbstract:The treatment of migraine is impeded by several difficulties, among which insufficient headache relief, side effects, and risk for developing medication overuse headache (MOH). Thus, new acutely acting Antimigraine Drugs are currently being developed, among which the small molecule CGRP receptor antagonists, gepants, and the 5-HT1F receptor agonist lasmiditan. Whether treatment with these Drugs carries the same risk for developing MOH is currently unknown. Pathophysiological studies on MOH in animal models have suggested that decreased 5-hydroxytryptamine (5-HT, serotonin) levels, increased calcitonin-gene related peptide (CGRP) expression and changes in 5-HT receptor expression (lower 5-HT1B/D and higher 5-HT2A expression) may be involved in MOH. The decreased 5-HT may increase cortical spreading depression frequency and induce central sensitization in the cerebral cortex and caudal nucleus of the trigeminal tract. Additionally, low concentrations of 5-HT, a feature often observed in MOH patients, could increase CGRP expression. This provides a possible link between the pathways of 5-HT and CGRP, targets of lasmiditan and gepants, respectively. Since lasmiditan is a 5-HT1F receptor agonist and gepants are CGRP receptor antagonists, they could have different risks for developing MOH because of the different (over) compensation mechanisms following prolonged agonist versus antagonist treatment. The acute treatment of migraine will certainly improve with the advent of two novel classes of Drugs, i.e., the 5-HT1F receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants). Data on the effects of 5-HT1F receptor agonism in relation to MOH, as well as the effects of chronic CGRP receptor blockade, are awaited with interest.
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a human trigeminovascular biomarker for Antimigraine Drugs a randomised double blind placebo controlled crossover trial with sumatriptan
Cephalalgia, 2017Co-Authors: Khalil Ibrahimi, Anton H Van Den Meiracker, Gisela M Terwindt, Alexander H. J. Danser, Antoinette MaassenvandenbrinkAbstract:Current Antimigraine Drugs are believed, besides their direct vasoconstrictive effect, to inhibit calcitonin gene-related peptide (CGRP) release from trigeminal nerve endings during migraine.Object...
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A human trigeminovascular biomarker for Antimigraine Drugs: A randomised, double-blind, placebo-controlled, crossover trial with sumatriptan.
Cephalalgia : an international journal of headache, 2016Co-Authors: Khalil Ibrahimi, Gisela M Terwindt, Alexander H. J. Danser, Ah Van Den Meiracker, Antoinette MaassenvandenbrinkAbstract:Current Antimigraine Drugs are believed, besides their direct vasoconstrictive effect, to inhibit calcitonin gene-related peptide (CGRP) release from trigeminal nerve endings during migraine. Objective The objective of this report is to establish a biomarker for the CGRP-interfering effect of Antimigraine Drugs. Methods We quantified the effect of sumatriptan on the trigeminal nerve-mediated rise in forehead dermal blood flow (DBF), induced by capsaicin application (0.6 mg/ml) and electrical stimulation (0.2-1.0 mA), in a randomised, double-blind, placebo-controlled, crossover study in healthy male ( n = 11, age ± SD: 29 ± 8 years) and female ( n = 11, 32 ± 7 years) individuals. Results DBF responses to capsaicin were attenuated by sumatriptan (ΔDBF, mean ± SEM: 82 ± 18 AU, p = 0.0002), but not by placebo (ΔDBF: 21 ± 12 AU, p = 0.1026). Conclusion We demonstrated that sumatriptan inhibits increases in DBF, induced by the release of, most likely, CGRP. Thus, our model may be used as a biomarker to establish the trigeminovascular effects of (potential) Antimigraine Drugs, such as CGRP receptor antagonists or antibodies directed against CGRP or its receptor.
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potential mechanisms of prospective Antimigraine Drugs a focus on vascular side effects
Pharmacology & Therapeutics, 2011Co-Authors: Kayi Y Chan, Steve Vermeersch, Jan De Hoon, Carlos M. Villalón, Antoinette MaassenvandenbrinkAbstract:Abstract Currently available Drugs for the acute treatment of migraine, i.e. ergot alkaloids and triptans, are cranial vasoconstrictors. Although cranial vasoconstriction is likely to mediate—at least a part of—their therapeutic effects, this property also causes vascular side-effects. Indeed, the ergot alkaloids and the triptans have been reported to induce myocardial ischemia and stroke, albeit in extremely rare cases, and are contraindicated in patients with known cardiovascular risk factors. In view of these limitations, novel Antimigraine Drugs devoid of vascular (side) effects are being explored. Currently, calcitonin gene-related peptide (CGRP) receptor antagonists, which do not have direct vasoconstrictor effects, are under clinical development. Other classes of Drugs, such as 5-HT 1F receptor agonists, glutamate receptor antagonists, nitric oxide synthase inhibitors, VPAC/PAC receptor antagonists and gap junction modulators, have also been proposed as potential targets for acute Antimigraine Drugs. Although these prospective Drugs do not directly induce vasoconstriction, they may well induce indirect vascular effects by inhibiting or otherwise modulating the responses to endogenous vasoactive substances. These indirect vascular effects might contribute to the therapeutic efficacy of the previously mentioned compounds, but may alternatively also lead to vascular side-effects. As described in the current review, some of the prospective Antimigraine Drugs with a proposed non-vascular mechanism of action may still have direct or indirect vascular effects.
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Effects of current and prospective Antimigraine Drugs on the porcine isolated meningeal artery
Naunyn-Schmiedeberg's Archives of Pharmacology, 2006Co-Authors: Suneet Mehrotra, Ad J.j.c. Bogers, Carlos M. Villalón, Ingrid M Garrelds, Saurabh Gupta, Antoinette MaassenvandenbrinkAbstract:Vasoconstriction to agonists at serotonin (5-hydroxytryptamine; 5-HT) receptors and α-adrenoceptors, as well as vasodilatation induced by α-CGRP, have been well described in the porcine carotid circulation in vivo. The present study sets out to investigate the effects of current and prospective Antimigraine Drugs on porcine meningeal artery segments in vitro. Sumatriptan, ergotamine, dihydroergotamine, isometheptene and clonidine failed to contract the meningeal artery, but 5-HT, noradrenaline and phenylephrine induced concentration-dependent contractions. The contractions to 5-HT were competitively antagonized by the 5-HT_2A receptor antagonist ketanserin, whilst those to noradrenaline were antagonized by α_1-(prazosin), α_2-(rauwolscine and yohimbine) and α_2C/2B-(OPC-28326) adrenoceptor antagonists. Whilst dobutamine and salbutamol were ineffective, α-CGRP produced concentration-dependent relaxations that were antagonized by the CGRP_1 receptor antagonist olcegepant. In agreement with their lack of contractile effect, sumatriptan and ergotamine failed to influence forskolin-stimulated cyclic AMP accumulation in the porcine meningeal artery; in contrast, both compounds decreased forskolin-stimulated cyclic AMP accumulation in the human isolated saphenous vein, where they induced contractions. Finally, using RT-PCR, we could demonstrate the presence of mRNAs encoding for several 5-HT receptors (5-HT_1B, 5-HT_1D, 5-HT_1F, 5-HT_2A and 5-HT_7) and adrenoceptors (α_1A, α_1B, α_1D, α_2A, α_2B, α_2C, β_1 and β_2), as well as that for the calcitonin receptor like receptor, a component of the CGRP_1 receptor. These results suggest that: (i) the porcine meningeal artery may not be involved in the vasoconstriction of the carotid vascular bed elicited by Antimigraine Drugs in anaesthetized pigs, and (ii) the mismatch between the presence of receptor mRNA and the lack of response to sumatriptan, dobutamine and salbutamol implies that mRNAs for the 5-HT_1B receptor and β_1- and β_2-adrenoceptors are probably unstable, or that their density is too low for being translated as receptor protein in sufficient quantities.
Richard Hargreaves - One of the best experts on this subject based on the ideXlab platform.
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differential effects of the 5ht1b 1d receptor agonist naratriptan on trigeminal versus spinal nociceptive responses
Cephalalgia, 1998Co-Authors: Michael J Cumberbatch, Raymond G. Hill, Richard HargreavesAbstract:In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist Antimigraine Drugs.
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Differential Effects of the 5Ht1B/1D Receptor Agonist Naratriptan on trigeminal Versus Spinal Nociceptive Responses
Cephalalgia, 1998Co-Authors: Michael J Cumberbatch, Raymond G. Hill, Richard HargreavesAbstract:In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist Antimigraine Drugs.
James T. Stewart - One of the best experts on this subject based on the ideXlab platform.
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Determination of Antimigraine compounds rizatriptan, zolmitriptan, naratriptan and sumatriptan in human serum by liquid chromatography/electrospray tandem mass spectrometry.
Rapid Communications in Mass Spectrometry, 2000Co-Authors: Karthick Vishwanathan, Michael G Bartlett, James T. StewartAbstract:Development of a rapid, sensitive and selective method for the determination of Antimigraine Drugs from human serum is essential for understanding the pharmacokinetics of these Drugs when administered concurrently. Solid phase extraction (SPE) using Oasis HLB was used to extract the Drugs (sumatriptan, naratriptan, zolmitriptan and rizatriptan) and the internal standard bufotenine from serum. A method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated to simultaneously quantitate these Antimigraine Drugs from human serum. The precursor and major product ions of the analytes were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The base peak in all the analytes is formed by alpha cleavage associated with protonation of the secondary amine. Mechanisms for the formation of the collision-induced dissociation products of these Antimigraine compounds are proposed. Linear calibration curves were generated from 1-100 ng/mL with all coefficients of determination greater than 0.99. The inter- and intraday precision (%RSD) were less than 9.3% and accuracy (%error) was less than 9.8% for all components. The limits of detection (LOD) for the method were 250 pg/mL for sumatriptan and 100 pg/mL for the remaining analytes based on a signal-to-noise ratio of 3.
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determination of Antimigraine compounds rizatriptan zolmitriptan naratriptan and sumatriptan in human serum by liquid chromatography electrospray tandem mass spectrometry
Rapid Communications in Mass Spectrometry, 2000Co-Authors: Karthick Vishwanathan, Michael G Bartlett, James T. StewartAbstract:Development of a rapid, sensitive and selective method for the determination of Antimigraine Drugs from human serum is essential for understanding the pharmacokinetics of these Drugs when administered concurrently. Solid phase extraction (SPE) using Oasis HLB was used to extract the Drugs (sumatriptan, naratriptan, zolmitriptan and rizatriptan) and the internal standard bufotenine from serum. A method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated to simultaneously quantitate these Antimigraine Drugs from human serum. The precursor and major product ions of the analytes were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The base peak in all the analytes is formed by alpha cleavage associated with protonation of the secondary amine. Mechanisms for the formation of the collision-induced dissociation products of these Antimigraine compounds are proposed. Linear calibration curves were generated from 1–100 ng/mL with all coefficients of determination greater than 0.99. The inter- and intraday precision (%RSD) were less than 9.3% and accuracy (%error) was less than 9.8% for all components. The limits of detection (LOD) for the method were 250 pg/mL for sumatriptan and 100 pg/mL for the remaining analytes based on a signal-to-noise ratio of 3. Copyright © 2000 John Wiley & Sons, Ltd.
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Determination of Antimigraine compounds rizatriptan, zolmitriptan, naratriptan and sumatriptan in human serum by liquid chromatography/electrospray tandem mass spectrometry.
Rapid Communications in Mass Spectrometry, 2000Co-Authors: Karthick Vishwanathan, Michael G Bartlett, James T. StewartAbstract:Development of a rapid, sensitive and selective method for the determination of Antimigraine Drugs from human serum is essential for understanding the pharmacokinetics of these Drugs when administered concurrently. Solid phase extraction (SPE) using Oasis HLB was used to extract the Drugs (sumatriptan, naratriptan, zolmitriptan and rizatriptan) and the internal standard bufotenine from serum. A method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated to simultaneously quantitate these Antimigraine Drugs from human serum. The precursor and major product ions of the analytes were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The base peak in all the analytes is formed by alpha cleavage associated with protonation of the secondary amine. Mechanisms for the formation of the collision-induced dissociation products of these Antimigraine compounds are proposed. Linear calibration curves were generated from 1–100 ng/mL with all coefficients of determination greater than 0.99. The inter- and intraday precision (%RSD) were less than 9.3% and accuracy (%error) was less than 9.8% for all components. The limits of detection (LOD) for the method were 250 pg/mL for sumatriptan and 100 pg/mL for the remaining analytes based on a signal-to-noise ratio of 3. Copyright © 2000 John Wiley & Sons, Ltd.
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determination of Antimigraine compounds rizatriptan zolmitriptan naratriptan and sumatriptan in human serum by liquid chromatography electrospray tandem mass spectrometry
Rapid Communications in Mass Spectrometry, 2000Co-Authors: Karthick Vishwanathan, Michael G Bartlett, James T. StewartAbstract:Development of a rapid, sensitive and selective method for the determination of Antimigraine Drugs from human serum is essential for understanding the pharmacokinetics of these Drugs when administered concurrently. Solid phase extraction (SPE) using Oasis HLB was used to extract the Drugs (sumatriptan, naratriptan, zolmitriptan and rizatriptan) and the internal standard bufotenine from serum. A method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated to simultaneously quantitate these Antimigraine Drugs from human serum. The precursor and major product ions of the analytes were monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The base peak in all the analytes is formed by alpha cleavage associated with protonation of the secondary amine. Mechanisms for the formation of the collision-induced dissociation products of these Antimigraine compounds are proposed. Linear calibration curves were generated from 1-100 ng/mL with all coefficients of determination greater than 0.99. The inter- and intraday precision (%RSD) were less than 9.3% and accuracy (%error) was less than 9.8% for all components. The limits of detection (LOD) for the method were 250 pg/mL for sumatriptan and 100 pg/mL for the remaining analytes based on a signal-to-noise ratio of 3.
Michael J Cumberbatch - One of the best experts on this subject based on the ideXlab platform.
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differential effects of the 5ht1b 1d receptor agonist naratriptan on trigeminal versus spinal nociceptive responses
Cephalalgia, 1998Co-Authors: Michael J Cumberbatch, Raymond G. Hill, Richard HargreavesAbstract:In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist Antimigraine Drugs.
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Differential Effects of the 5Ht1B/1D Receptor Agonist Naratriptan on trigeminal Versus Spinal Nociceptive Responses
Cephalalgia, 1998Co-Authors: Michael J Cumberbatch, Raymond G. Hill, Richard HargreavesAbstract:In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist Antimigraine Drugs.
