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a pretreatment with methadone but not with morphine produced a cross-desensitization with [D-Ala 2 , D-Leu 5 ]-enkephalin (DADLE) and morphine (Liu et al., 2 -D-Pen 5 ]-enkephalin (DPDPE) and deltorphin I (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH 2 ) induced a stronger and faster desensitization compared to the alkaloid agonist etorphine (Allouche et al., 5 ]- and [Met 5 ]-enkephalins and UFP-512 ([H-Dmt-Tic-NH-CH(CH 2 -COOH)-Bid])) and non-peptidic (SNC-80 ((+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide) and ARM-390) ligands we didn't confirm such assumption but our data rather suggest that DOR selective agonists promote profound desensitization compared to non-selective ligands (Marie et al., Biased agonism at KOR and desensitization Very few studies examined the regulation of KOR by different agonists

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