Systemic effects of E-2078, a stabilized dynorphin A(1–8) analog, in rhesus monkeys
dc.contributor.author | Woods, James H. | en_US |
dc.contributor.author | Yu, Jim | en_US |
dc.contributor.author | Butelman, Eduardo R. | en_US |
dc.contributor.author | Kreek, Mary-Jeanne | en_US |
dc.contributor.author | Vivian, Jeffrey A. | en_US |
dc.date.accessioned | 2006-09-08T19:49:30Z | |
dc.date.available | 2006-09-08T19:49:30Z | |
dc.date.issued | 1999-04 | en_US |
dc.identifier.citation | Butelman, E. R.; Vivian, Jeffrey A.; Yu, J.; Kreek, Mary-Jeanne; Woods, James H.; (1999). "Systemic effects of E-2078, a stabilized dynorphin A(1–8) analog, in rhesus monkeys." Psychopharmacology 143(2): 190-196. <http://hdl.handle.net/2027.42/41963> | en_US |
dc.identifier.issn | 0033-3158 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/41963 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10326782&dopt=citation | en_US |
dc.description.abstract | Rationale : E-2078 ([ N -methyl-Tyr 1 , N -methyl-Arg 7 , d -Leu 8 ] dynorphin A(1–8) ethylamide) is a dynorphin A(1–8) analog with a reduced tendency to be biotransformed, when compared to the unmodified opioid peptide. E-2078 has been found to produce κ-opioid agonist effects in vivo in rodents. Objective : In the present studies, we investigated whether systemically administered E-2078 could produce κ-agonist effects in rhesus monkeys, in tests of antinociception, diuresis and ethylketocyclazocine (EKC) discrimination. Methods : E-2078 (0.32–18 mg/kg, SC, IM or IV) was tested in the warm water (50°, 55°C) tail withdrawal assay of thermal antinociception. The diuretic effects of E-2078 (0.056– 1.8 mg/kg, SC) were also compared to those of the κ-agonist, U69,593 (0.01–0.32 mg/kg, SC). Lastly, the effects of E-2078 (0.1–3.2 mg/kg, SC or IV) were studied in rhesus monkeys trained to discriminate EKC (0.0056 mg/kg SC) from vehicle, in a food-reinforced operant procedure. Results : E-2078 did not produce thermal antinociception in rhesus monkeys following SC or IM administration, up to the largest doses presently studied (i.e., 18 and 10 mg/kg, respectively). E-2078 caused thermal antinociception by the IV route, but this effect was not apparently mediated by κ- or µ-opioid receptors, as shown by its insensitivity to quadazocine (1 mg/kg) pretreatment. However, SC E-2078 caused diuresis, and this effect was blocked by quadazocine pretreatment, consistent with mediation by κ-opioid receptors. E-2078 generalized in EKC-discriminating monkeys, but only after the largest dose (3.2 mg/kg), and only following IV administration. Conclusions : The present studies suggest that systemically administered E-2078 can produce some κ-receptor mediated effects in rhesus monkeys, but its profile of action is not identical to non-peptidic κ-agonists following all routes of administration, or across all experimental situations. | en_US |
dc.format.extent | 100791 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Springer-Verlag; Springer-Verlag Berlin Heidelberg | en_US |
dc.subject.other | Legacy | en_US |
dc.subject.other | Key Words Antinociception | en_US |
dc.subject.other | Macaca Mulatta | en_US |
dc.subject.other | Diuresis | en_US |
dc.subject.other | κ-Opioid Receptors | en_US |
dc.title | Systemic effects of E-2078, a stabilized dynorphin A(1–8) analog, in rhesus monkeys | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Psychiatry | en_US |
dc.subject.hlbsecondlevel | Neurosciences | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109, USA, US, | en_US |
dc.contributor.affiliationum | Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109, USA, US, | en_US |
dc.contributor.affiliationother | Rockefeller University (Box 171), 1230 York Ave, New York, NY 10021, USA, e-mail: butelme@rockvax.rockefeller.edu, Fax: +1-212-327-8574, US, | en_US |
dc.contributor.affiliationother | Rockefeller University (Box 171), 1230 York Ave, New York, NY 10021, USA, e-mail: butelme@rockvax.rockefeller.edu, Fax: +1-212-327-8574, US, | en_US |
dc.contributor.affiliationother | Rockefeller University (Box 171), 1230 York Ave, New York, NY 10021, USA, e-mail: butelme@rockvax.rockefeller.edu, Fax: +1-212-327-8574, US, | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 10326782 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/41963/1/213-143-2-190_91430190.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/s002130050935 | en_US |
dc.identifier.source | Psychopharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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