title: Partial and full agonism in endomorphin derivatives: comparison by null and operational model.
abstract: The partial mu-opioid receptor pool inactivation strategy in isolated mouse vas deferens was used to determine partial agonism of endomorphins and their analogs (endomorphin-1-ol, 2',6'-dimethyltyrosine (Dmt)-endomorphin-1, endomorphin-2-ol and (D-Met2)-endomorphin-2) using morphine, normorphine, morphiceptin, (D-Ala2,MePhe4,Gly5-ol)-enkephalin (DAMGO) and its amide (DAMGA) as reference opioid agonists. Agonist affinities (KA) and efficacies were assessed both by the "null" and the "operational" method. The KA values determined by the two methods correlated significantly with each other and also with the displacing potencies against 3H-naloxone in the receptor binding assay in the presence of Na+. DAMGO and DAMGA were full agonist prototypes, morphine, endomorphin-1, endomorphin-1-ol, Dmt-endomorphin-1, endomorphin-2-ol and (D-Met2)-endomorphin-2 were found by both methods to be partial agonists whereas the parameters for normorphine, morphiceptin and endomorphin-2 were intermediate.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, PO Box 370, H-1445 Budapest, Hungary. ronand@pharma.sote.hu
authors.forename: András Z
authors.initials: AZ
authors.lastname: Rónai
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Khrasani
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
authors.forename: Imre
authors.initials: I
authors.lastname: Lengyel
authors.forename: László
authors.initials: L
authors.lastname: Kocsis
authors.forename: György
authors.initials: G
authors.lastname: Orosz
authors.forename: Géza
authors.initials: G
authors.lastname: Tóth
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Kató
authors.forename: László
authors.initials: L
authors.lastname: Tóthfalusi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000737:chemistry; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D009022:Morphine Derivatives / Q000737:chemistry; D009270:Naloxone / Q000737:chemistry; D009842:Oligopeptides / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014649:Vas Deferens / Q000378:metabolism
chemical_list: D004723:Endorphins; D009022:Morphine Derivatives; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C512611:enkephalin, Ala(2)-MePhe(4)-GlyNH2(5)-; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C105294:endomorphin 2; C028889:morphiceptin; C010616:normorphine