{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T01:15:09Z","timestamp":1774660509164,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The novel endogenous \u03bc -opioid receptor (MOR) agonists endomorphin 1 (EM1) and 2 (EM2) were tested for their cardiorespiratory effects in conscious, freely behaving rats. After systemic (intravenous) administration of EM1, EM2, or the selective MOR agonist DAMGO, analgesia, minute ventilation (V\u02d9e), heart rate (HR) and mean arterial blood pressure (BP) were measured. The threshold dose for analgesia was similar for all 3 peptides (\u223c 900 nmol\/kg). All 3 compounds elicited biphasic V\u02d9e responses, with marked, short-lived V\u02d9e depressions (4\u20136 s) followed by more sustained V\u02d9e increases (10\u201312 min). However, compared with responses elicited by EM2 or DAMGO, EM1 decreased V\u02d9e only at higher doses, and produced greater V\u02d9e stimulation. Morphine produced a V\u02d9e decrease, but no subsequent V\u02d9e increase. EM2 and DAMGO decreased HR and BP, while EM1 decreased HR, but did not decrease BP in conscious rats at doses up to 9,600 nmol\/kg. In anesthetized rats, all 3 peptides decreased HR and BP. The decreases in V\u02d9e, HR, and BP were blocked by the MOR antagonist, naloxone HCI (NIx). Only the HR and BP responses, however, were blocked by naloxone-methiodide (MeNIx), indicating central mediation of V\u02d9e responses and peripheral mediation of cardiovascular responses. We conclude that MOR-selective compounds vary in their cardiorespiratory response characteristics which could be linked to differential cellular actions. The results support the concept that the analgesic, respiratory, and cardiovascular effects of MOR agonists can be dissociated and that EM1-like compounds could provide the basis for novel, safer analgesics.<\/jats:p>","DOI":"10.1164\/ajrccm.162.3.9911102","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:23:40Z","timestamp":1365085420000},"page":"994-999","source":"Crossref","is-referenced-by-count":100,"title":["Differential Cardiorespiratory Effects of Endomorphin 1, Endomorphin 2, DAMGO, and Morphine"],"prefix":"10.1093","volume":"162","author":[{"given":"MARC A.","family":"CZAPLA","sequence":"first","affiliation":[{"name":"Constance S. Kaufman Pediatric Pulmonary Research Laboratory and Departments of Pediatrics, Physiology, Neuroscience, and Medicine, Tulane University School of Medicine, and Veterans Affairs Medical Center, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DAVID","family":"GOZAL","sequence":"additional","affiliation":[{"name":"Constance S. Kaufman Pediatric Pulmonary Research Laboratory and Departments of Pediatrics, Physiology, Neuroscience, and Medicine, Tulane University School of Medicine, and Veterans Affairs Medical Center, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"OSCAR A.","family":"ALEA","sequence":"additional","affiliation":[{"name":"Constance S. Kaufman Pediatric Pulmonary Research Laboratory and Departments of Pediatrics, Physiology, Neuroscience, and Medicine, Tulane University School of Medicine, and Veterans Affairs Medical Center, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ROBERT C.","family":"BECKERMAN","sequence":"additional","affiliation":[{"name":"Constance S. Kaufman Pediatric Pulmonary Research Laboratory and Departments of Pediatrics, Physiology, Neuroscience, and Medicine, Tulane University School of Medicine, and Veterans Affairs Medical Center, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JAMES E.","family":"ZADINA","sequence":"additional","affiliation":[{"name":"Constance S. Kaufman Pediatric Pulmonary Research Laboratory and Departments of Pediatrics, Physiology, Neuroscience, and Medicine, Tulane University School of Medicine, and Veterans Affairs Medical Center, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,9,1]]},"reference":[{"key":"2026032708283989700_B1"},{"key":"2026032708283989700_B2","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1152\/jappl.1985.59.6.1675","article-title":"Opioids and breathing.","volume":"59","author":"Santiago","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"2026032708283989700_B3"},{"key":"2026032708283989700_B4","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S0022-3565(25)31491-6","article-title":"Alterations in the antagonism by naloxone of morphine-induced respiratory depression and analgesia after morphine pretreatment.","volume":"207","author":"McGilliard","year":"1978","journal-title":"J. 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