PT  - JOURNAL ARTICLE
AU  - Camilla I. Svensson
AU  - Yosup Rew
AU  - Shelle Malkmus
AU  - Peter W. Schiller
AU  - Joseph P. Taulane
AU  - Murray Goodman
AU  - Tony L. Yaksh
TI  - Systemic and Spinal Analgesic Activity of a δ-Opioid-Selective Lanthionine Enkephalin Analog
AID  - 10.1124/jpet.102.039750
DP  - 2003 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 827--832
VI  - 304
IP  - 2
4099  - http://jpet.aspetjournals.org/content/304/2/827.short
4100  - http://jpet.aspetjournals.org/content/304/2/827.full
SO  - J Pharmacol Exp Ther2003 Feb 01; 304
AB  - A lanthionine enkephalin derivative, Tyr-c[d-ValL-Gly-Phe-d-AlaL]-OH (DVL2DAL5LanEnk), where ValL and AlaL denote the lanthionine amino acid ends linked via a monosulfide bridge to form the lanthionine structure, was synthesized. It was found to possess selectivity for and potency at the δ versus μ opioid receptor as defined by binding studies and by its respective activity on the mouse vas deferens compared with the guinea pig ileum. The agent produced a potent analgesia after intrathecal and intraperitoneal delivery with ED50 values being, respectively, 0.19 μg and 0.49 mg/kg. The effects of the agent were reversed by the δ-selective antagonist naltrindole. These analgesic actions occurred at doses that had no effect upon general behavior or motor function. These results suggest a potent δ-preferring agent suitable for development as a systemic δ opioid analgesic. The American Society for Pharmacology and Experimental Therapeutics