Journal article
Systemic analgesic activity and .delta.-opioid selectivity in [2,6-dimethyl-Tyr1, D-Pen2, D-Pen5]enkephalin
Journal of medicinal chemistry, Vol.35(4), pp.684-687
02/01/1992
DOI: 10.1021/jm00082a008
PMID: 1311764
Abstract
The cyclic peptide [2,6-dimethyl-Tyr1,D-Pen2,D-Pen5]enkephalin (2) was synthesized by solid-phase techniques and contains the optically pure unnatural amino acid 2,6-dimethyltyrosine (DMT) as a replacement for the Tyr1 residue of [D-Pen2,D-Pen8]enkephalin (DPDPE, 1). This structural modification resulted in a 10-fold increase in the potency of 2 at the δ opioid receptor and a 35-fold increase in potency at the μ receptor while substantial δ receptor selectivity was maintained. In addition, 2 was 86-fold more effective than 1 at inhibiting electrically stimulated contractions of the mouse vas deferens. In the hot plate test, 2 was 7-fold more potent than 1 after intracerebroventricular administration in the mouse. While 1 was inactive following systemic administration of doses as high as 30 mg/kg, subcutaneous administration of 2 significantly inhibited writhing with an EDM of 2.6 mg/kg. These results demonstrate that the potency and systemic activity of DPDPE are significantly increased by replacement of Tyr1 with DMT.
Details
- Title: Subtitle
- Systemic analgesic activity and .delta.-opioid selectivity in [2,6-dimethyl-Tyr1, D-Pen2, D-Pen5]enkephalin
- Creators
- Donald W HansenAwilda StapelfeldMichael A SavageMelvin ReichmanDonna L HammondRonald C HaasethHenry I Mosberg
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.35(4), pp.684-687
- DOI
- 10.1021/jm00082a008
- PMID
- 1311764
- NLM abbreviation
- J Med Chem
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Publisher
- American Chemical Society
- Language
- English
- Date published
- 02/01/1992
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006430902771
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