Abstract

The overall goal of this Core Facility is to perform preclinical toxicological studies on two potent delta opioid receptor antagonists c[D-Pen2,D-Pen5]enkephalin (DPDPE) and biphalin, to prepare sterile pyrogen free injectable DPDPE and biphalin solution for preclinical toxicological studies at The University of Arizona and by Dr. Yaksh at the University of San Diego. Specifically, we will perform intravenous acute toxicology studies for DPDPE and biphalin in rats and dogs giving daily i.v. injections of either agent or 30 and 5 days, respectively. At the end of dosing the animals will be euthanized and organs will be collected, weighed and tissue slices prepared for blinded histopathological studies. If not toxic, the data from these studies will be combined with the I.T. toxicological studies of Dr. Yaksh and incorporated into an investigator-sponsored investigational New Drug Application (INDA) for each agent.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
5P01DA006284-11
Application #
6300727
Study Section
Project Start
2000-04-01
Project End
2001-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
11
Fiscal Year
2000
Total Cost
$104,534
Indirect Cost

  Institution

Name
University of Arizona
Department
Type
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721

  Publications

Remesic, Michael; Macedonio, Giorgia; Mollica, Adriano et al. (2018) Cyclic biphalin analogues with a novel linker lead to potent agonist activities at mu, delta, and kappa opioid receptors. Bioorg Med Chem 26:3664-3667
Mowlazadeh Haghighi, Saghar; Zhou, Yang; Dai, Jixun et al. (2018) Replacement of Arg with Nle and modified D-Phe in the core sequence of MSHs, Ac-His-D-Phe-Arg-Trp-NH2, leads to hMC1R selectivity and pigmentation. Eur J Med Chem 151:815-823
Sandweiss, A J; McIntosh, M I; Moutal, A et al. (2018) Genetic and pharmacological antagonism of NK1 receptor prevents opiate abuse potential. Mol Psychiatry 23:1745-1755
Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita et al. (2017) Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain. Pain 158:2386-2395
Vardanyan, Ruben S; Cain, James P; Haghighi, Saghar Mowlazadeh et al. (2017) Synthesis and Investigation of Mixed ?-Opioid and ?-Opioid Agonists as Possible Bivalent Ligands for Treatment of Pain. J Heterocycl Chem 54:1228-1235
Cai, Minying; Marelli, Udaya Kiran; Mertz, Blake et al. (2017) Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists. Biochemistry 56:4201-4209
Remesic, Michael; Lee, Yeon Sun; Hruby, Victor J (2016) Cyclic Opioid Peptides. Curr Med Chem 23:1288-303
Ramos-Colon, Cyf N; Lee, Yeon Sun; Remesic, Michael et al. (2016) Structure-Activity Relationships of [des-Arg7]Dynorphin A Analogues at the ? Opioid Receptor. J Med Chem 59:10291-10298
Hall, Sara M; Lee, Yeon Sun; Hruby, Victor J (2016) Dynorphin A analogs for the treatment of chronic neuropathic pain. Future Med Chem 8:165-77
Deekonda, Srinivas; Cole, Jacob; Sunna, Sydney et al. (2016) Enkephalin analogues with N-phenyl-N-(piperidin-2-ylmethyl)propionamide derivatives: Synthesis and biological evaluations. Bioorg Med Chem Lett 26:222-7

Showing the most recent 10 out of 268 publications