{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:47:02Z","timestamp":1792018022271,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T00:00:00Z","timestamp":1166400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A combination of midodrine and dihydroergotamine (DHE) is frequently used clinically in patients suffering from severe orthostatic hypotension (OH). Whereas midodrine acts as a selective, peripheral alpha1\u2010receptor agonist, DHE displays complex pharmacology and can behave as an alpha\u2010adrenergic receptor agonist or antagonist. Surprisingly, the consequences of such a combination on blood pressure have never been investigated. The present study was performed in order to evaluate the pressor effects induced by the administration of both midodrine and DHE in old conscious dogs (<jats:italic>n<\/jats:italic>\u2003=\u20036) in experimental condition reproducing autonomic failure\u2010related baroreflex dysfunction (atropine 0.1\u2003mg\/kg). For this purpose, we first studied the relative potency and intrinsic activity of each agonist and noradrenaline (NA) for the alpha1\u2010adrenergic receptor. The orders of potency obtained in our study were 0.35, 11 and 400\u2003<jats:italic>\u03bc<\/jats:italic>g\/kg for NA, DHE and midodrine, and intrinsic activity: NA\u2003&gt;\u2003midodrine\u2003&gt;\u2003DHE. These results strongly suggest that DHE really acts in vivo as an alpha1\u2010adrenoceptor partial agonist. Afterwards, the pressor effects of coadministration of midodrine (0.4\u2003mg\/kg) and DHE (15\u2003<jats:italic>\u03bc<\/jats:italic>g\/kg) were investigated: in one setting, midodrine was first administered, followed by DHE; in another, DHE was first administered, followed by midodrine. Our results show that in conscious dogs, the combination of midodrine and DHE leads to near\u2010complete abolition of the pressor effect induced by the first administered drug. This in vivo proof of such antagonistic effects on blood pressure could explain clinical observations of worsening of OH in humans administered midodrine plus DHE. Although in vivo results obtained in conscious healthy dogs need to be experimentally and clinically confirmed in humans suffering from OH, these results strongly suggest that a midodrine\u2013DHE combined treatment should be avoided in clinical practice.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2006.00450.x","type":"journal-article","created":{"date-parts":[[2006,12,20]],"date-time":"2006-12-20T10:52:37Z","timestamp":1166611957000},"page":"45-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In vivo pharmacodynamic interactions between two drugs used in orthostatic hypotension \u2013 midodrine and dihydroergotamine"],"prefix":"10.1111","volume":"21","author":[{"given":"G\u00e9raldine","family":"Jourdan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Verwaerde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Antoinette","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Montastruc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Senard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12,18]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.5.1470"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.19.6.508"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1996.tb03738.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01081.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-137-9-200211050-00011"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004150050407"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000106629"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(99)00257-5"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.21.2290"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.2.3.393"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(02)00213-8"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-199812010-00007"},{"key":"e_1_2_6_14_2","first-page":"613","article-title":"Etude des pratiques de prescriptions de midodrine (Gutron) dans un centre Hospitalier Universitaire","volume":"55","author":"Desboeuf K.","year":"2000","journal-title":"Th\u00e9rapie"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00626-8"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1001\/jama.1997.03540370036033","article-title":"Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. 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