caa a22 4500 46911861X CHVBK 20180323133131.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF02245876 doi (NATIONALLICENCE)springer-10.1007/BF02245876 Pharmacological profile of a potent, efficacious fentanyl derivative in rhesus monkeys [Elektronische Daten] [C. France, G. Winger, M. Seggel, K. Rice, J. Woods] The recent synthesis of fentanyl derivatives, some of which appear to have novel profiles of pharmacological effects, has provided compelling evidence that μ opioid efficacy might be altered systematically by modifications in the parent compound fentanyl. In the present study a new 4-(heteroanilido)-piperidine, compound 28, was studied for its effects in rhesus monkeys. In self-administration studies compound 28 maintained rates of lever pressing similar to those maintained by alfentanil; the reinforcing effects of compound 28 were attenuated by the opioid antagonist quadazocine. In drug discrimination studies compound 28 did not substitute for the κ agonist ethylketocyclazocine and did substitute for the μ agonist alfentanil. In morphine-treated subjects discriminating between saline and naltrexone, compound 28 did not substitute for naltrexone; however, in morphine-abstinent subjects compound 28 reversed naltrexone lever responding. Moreover, this discriminative stimulus effect in morphine-abstinent subjects was antagonized by naltrexone and by quadazocine in a manner consistent with μ receptor mediation. Compound 28 also was an effective analgesic in a warm-water, tail-withdrawal procedure and it decreased markedly respiratory function. The analgesic effects as well as the respiratory depressant effects of compound 28 were antagonized by quadazocine. Together, these results show compound 28 to be a potent, efficacious μ agonist of similar potency to alfentanil. Large differences in apparent efficacy at μ receptors between compound 28 and another compound in this series (mirfentanil), clearly demonstrate that, within this chemical family, small chemical changes can confer significant differences in pharmacologic effect. Springer-Verlag, 1992 Opioid nationallicence Drug discrimination nationallicence Analgesia nationallicence Fentanyl nationallicence Rhesus monkey nationallicence Competitive antagonism nationallicence Respiratory function nationallicence Self administration nationallicence France C. Department of Pharmacology and Experimental Therapeutics, Louisiana State University, Medical Center, 1100 Florida Avenue, 70119, New Orleans, LA, USA aut Winger G. Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA aut Seggel M. Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA aut Rice K. Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA aut Woods J. Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA aut Psychopharmacology Springer-Verlag 109/3(1992-11-01), 291-298 0033-3158 109:3<291 1992 109 213 https://doi.org/10.1007/BF02245876 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245876 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- France C. Department of Pharmacology and Experimental Therapeutics, Louisiana State University, Medical Center, 1100 Florida Avenue, 70119, New Orleans, LA, USA aut NATIONALLICENCE 700 1- Winger G. Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA aut NATIONALLICENCE 700 1- Seggel M. Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Rice K. Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Woods J. Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 109/3(1992-11-01), 291-298 0033-3158 109:3<291 1992 109 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer