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      Neuroendocrine Response to the Serotonin Agonist M-Chlorophenylpiperazine in Women with Menstrual Status migrainosus

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          Abstract

          To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: –4, –6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times –30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan’s post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %Δ<sub>max</sub> plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT<sub>1</sub> and 5-HT<sub>2</sub> receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.

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          Most cited references 12

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          Migraine--current understanding and treatment.

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            Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry.

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              Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors.

              Radioligand binding studies were used to analyze the interactions of two novel anxiolytics, buspirone and TVX Q 7821, with a series of 10 neuronal membrane receptor sites. Buspirone (IC50 = 24 nM) and TVX Q 7821 (IC50 = 9.5 nM) display the highest affinity for 5-hydroxytryptamine1A (5-HT1A) binding sites labeled by 3H-8-hydroxy-2-(di-n-pro-pylamino) tetralin (DPAT). By contrast, buspirone is 16-fold weaker at dopamine (D2) receptors (IC50 = 380 nM), whereas TVX Q 7821 is 6-fold less potent at alpha-adrenergic1 sites (IC50 = 58 nM). At the other receptors studied, buspirone and TVX Q 7821 had similar pharmacological profiles. Both agents display moderate affinity for histamine (H1), alpha-adrenergic2, and 5-HT2 binding sites. The drugs are essentially inactive at 5-HT1B, calcium channel antagonist, muscarinic cholinergic, and benzodiazepine receptors. These results suggest that the anxiolytic effects of buspirone and TVX Q 7821 may be mediated by central 5-HT1A receptors.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2003
                July 2003
                18 July 2003
                : 78
                : 1
                : 52-60
                Affiliations
                aDepartment of Obstetric and Gynecology, IRCCS ‘San Matteo’, and bUniversity Center of Adaptive Disorders and Headache, University of Pavia, Pavia; cDepartment of Neurology, Headache Centre, IRCCS ‘C. Mondino Foundation’, and dChair of Neurology, University ‘La Sapienza’, Rome, Italy
                Article
                71706 Neuroendocrinology 2003;78:52–60
                10.1159/000071706
                12869800
                © 2003 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Tables: 1, References: 40, Pages: 9
                Categories
                Reproductive Neuroendocrinology

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