mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I).
Novel compounds were prepared that united the pharmacologies of the mu-opioid tramadol with the 5-HT4 agonists metoclopramide and norcisapride. The synthesis, chiral separation and in vitro activity of the new compounds is described.
Shao
Liming
L
Sepracor Inc., 84 Waterford Drive, Marlborough, MA 01752, USA. liming.shao@sepracor.com
Wang
Fengjiang
F
Hewitt
Michael C
MC
Barberich
Timothy J
TJ
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D020117:Cisapride / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D008787:Metoclopramide / Q000737:chemistry / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects; D058828:Serotonin 5-HT4 Receptor Agonists; D013237:Stereoisomerism; D014147:Tramadol / Q000737:chemistry
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D058828:Serotonin 5-HT4 Receptor Agonists; C072044:norcisapride; D044422:Receptors, Serotonin, 5-HT4; D014147:Tramadol; D008787:Metoclopramide; D020117:Cisapride