Partial and full agonism in endomorphin derivatives: comparison by null and operational model.
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.
Rónai
András Z
AZ
Department of Pharmacology and Pharmacotherapy, Semmelweis University, PO Box 370, H-1445 Budapest, Hungary. ronand@pharma.sote.hu
Al-Khrasani
Mahmoud
M
Benyhe
Sándor
S
Lengyel
Imre
I
Kocsis
László
L
Orosz
György
G
Tóth
Géza
G
Kató
Erzsébet
E
Tóthfalusi
László
L
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
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