{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:31:08Z","timestamp":1790947868117,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114\u20102314\u2010B\u2010039\u2010047\u2010"],"award-info":[{"award-number":["NSTC 114\u20102314\u2010B\u2010039\u2010047\u2010"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114\u20102314\u2010B\u2010039\u2010038\u2010MY2"],"award-info":[{"award-number":["NSTC 114\u20102314\u2010B\u2010039\u2010038\u2010MY2"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR\u2010113\u2010207"],"award-info":[{"award-number":["DMR\u2010113\u2010207"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The aim of this study was to examine the effects of intrathecal lidocaine combined with guanfacine or dexmedetomidine on nociceptive and motor blockade, in comparison to clonidine. Using a rat model of intrathecal injection, we evaluated the effects of lidocaine combined with guanfacine, dexmedetomidine, or clonidine on nociceptive and motor blockade. The dose\u2010dependent effects of guanfacine on spinal nociceptive and motor blockade were compared to those of lidocaine, a well\u2010known local anesthetic. Guanfacine (0.46\u2009\u03bcmol\/kg, 3\u2009mM), dexmedetomidine (0.02\u2009\u03bcmol\/kg, 0.1\u2009mM), or clonidine (1.52\u2009\u03bcmol\/kg, 10\u2009mM) alone produced no spinal nociceptive or motor blockade. Co\u2010administration of guanfacine (0.46\u2009\u03bcmol\/kg) or dexmedetomidine (0.02\u2009\u03bcmol\/kg) with lidocaine (3.14 or 8.38\u2009\u03bcmol\/kg) prolonged the duration of spinal blockade, an effect attenuated by yohimbine (0.76\u2009\u03bcmol\/kg), which alone produced no spinal nociceptive or motor blockade. In contrast, the addition of clonidine (1.52\u2009\u03bcmol\/kg) did not enhance the duration of lidocaine\u2010induced spinal blockade. Guanfacine produced a dose\u2010dependent spinal blockade of both nociceptive and motor functions. The potency ranking (ED\n                    <jats:sub>50<\/jats:sub>\n                    , 50% effective dose) of spinal blockade showed that guanfacine and lidocaine were equal. Guanfacine resulted in a markedly longer spinal block duration than lidocaine at equivalent anesthetic doses (ED\n                    <jats:sub>25<\/jats:sub>\n                    , ED\n                    <jats:sub>50<\/jats:sub>\n                    , and ED\n                    <jats:sub>75<\/jats:sub>\n                    ). In summary, co\u2010administration of subeffective doses of guanfacine or dexmedetomidine with lidocaine prolonged the duration of spinal blockade, likely involving \u03b12\u2010adrenergic receptors, whereas subeffective doses of clonidine did not. Guanfacine produced dose\u2010dependent spinal blockade and was equipotent to lidocaine. At equianesthetic doses, guanfacine produced a longer duration of blockade than lidocaine.\n                  <\/jats:p>","DOI":"10.1111\/fcp.70057","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T05:30:03Z","timestamp":1763703003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Analysis of Intrathecal Lidocaine Combined With Guanfacine or Dexmedetomidine on Nociceptive and Motor Blockade in Rats"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1372-0245","authenticated-orcid":false,"given":"An\u2010Kuo","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Anesthesiology China Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, College of Medicine China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong\u2010Chi","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of General Surgery &amp; Department of Medical Education and Research, E\u2010Da Cancer Hospital I\u2010Shou University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine I\u2010Shou University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-2127","authenticated-orcid":false,"given":"Yu\u2010Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chi Mei Medical Center  Tainan Taiwan"},{"name":"Department of Physical Therapy, College of Health Care China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-4342","authenticated-orcid":false,"given":"Ching\u2010Hsia","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Medicine National Cheng Kung University  Tainan Taiwan"},{"name":"Institute of Allied Health Sciences, College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhi\u2010Joung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chi Mei Medical Center  Tainan Taiwan"},{"name":"Department of Anesthesiology Tri\u2010Service General Hospital &amp; National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S211234"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0375-9393.17.12283-2"},{"key":"e_1_2_10_4_1","article-title":"Bradycardia, Hypotension, and Cardiac Arrest: A Complication of Local Anesthetics","volume":"11","author":"Balasanmugam C.","year":"2019","journal-title":"Cureus"},{"key":"e_1_2_10_5_1","article-title":"Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine With Clonidine in Spinal Anaesthesia","volume":"10","author":"Wahi A.","year":"2016","journal-title":"Journal of Clinical and Diagnostic Research"},{"key":"e_1_2_10_6_1","first-page":"79","article-title":"Guanfacine and Clonidine: The Effects on Adrenal Medullary Function in Spontaneously Hypertensive Rats","volume":"272","author":"Togashi H.","year":"1984","journal-title":"Archives Internationales de Pharmacodynamie et de Th\u00e9rapie"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650.2019.1605076"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCE.0000000000000785"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2201"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-023-00458-4"},{"key":"e_1_2_10_11_1","first-page":"295","article-title":"The Alpha 2\u2010Adrenergic Agonists Clonidine and Guanfacine Produce Tonic and Phasic Block of Conduction in Rat Sciatic Nerve Fibers","volume":"76","author":"Butterworth J. 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