BIOMAT Database Logo BIOMAT Database Logo

Distribution and analgesia of [3H][D-Pen2, D-Pen5]enkephalin and two halogenated analogs after intravenous administration. 1991

S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Department of Pharmacology, University of Arizona, Tucson.

To improve pharmacological characteristics of the delta-selective, cyclic peptide [D-Pen2, D-Pen5]enkephalin (DPDPE), modification by halogenation at the Phe4 residue was undertaken. The present study was to determine the extent [3H]DPDPE, [3H][p-Cl-Phe4]DPDPE and [p-125IPhe4]DPDPE crosses the blood-brain barrier, elicits analgesia and to characterize selective organ distribution and stability after i.v. administration. A significantly greater percentage of total [3H][p-Cl-Phe4]DPDPE reached the brain after 10, 20 and 40 min as compared to [3H]DPDPE and both peptides were significantly displaced by pretreatment with naloxone or naltrindole. The amount of [3H]DPDPE detected in the brain was greater than that of [p-125IPhe4]DPDPE. Distribution results revealed large amounts of the administered peptides were sequestered rapidly in the gall bladder and secreted into the small intestine. Hot-plate antinociception tests 5 min after i.v. administration (30 and 60 mg/kg) revealed [p-Cl-Phe4]DPDPE to elicit a much greater analgesic effect as compared to DPDPE or [p-125IPhe4]DPDPE. These results provide evidence that [p-Cl-Phe4]DPDPE has a greater apparent distribution to the brain and has a greater effect on the antinociception threshold as tested on the hot-plate than DPDPE or [p-125IPhe4]DPDPE. Stability of unlabeled and tritiated DPDPE and [p-Cl-Phe4]DPDPE was determined both in vitro and in vivo; both unlabeled and tritiated DPDPE and [p-Cl-Phe4]DPDPE remain intact.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009019 Morphinans Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS. Morphinan
D009270 Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. MRZ 2593-Br,MRZ-2593,Nalone,Naloxon Curamed,Naloxon-Ratiopharm,Naloxone Abello,Naloxone Hydrobromide,Naloxone Hydrochloride,Naloxone Hydrochloride Dihydride,Naloxone Hydrochloride, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Naloxone, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Narcan,Narcanti,Abello, Naloxone,Curamed, Naloxon,Dihydride, Naloxone Hydrochloride,Hydrobromide, Naloxone,Hydrochloride Dihydride, Naloxone,Hydrochloride, Naloxone,MRZ 2593,MRZ 2593 Br,MRZ 2593Br,MRZ2593,Naloxon Ratiopharm
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004745 Enkephalins One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. Enkephalin
D000700 Analgesics Compounds capable of relieving pain without the loss of CONSCIOUSNESS. Analgesic,Anodynes,Antinociceptive Agents,Analgesic Agents,Analgesic Drugs,Agents, Analgesic,Agents, Antinociceptive,Drugs, Analgesic

Related Publications

S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
The mu-opioid receptor is necessary for [D-Pen2,D-Pen5]enkephalin-induced analgesia.
April 1997, European journal of pharmacology,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Theoretical study of the flexibility and solution conformation of the cyclic opioid peptides [D-Pen2,D-Pen5]enkephalin and [D-Pen2,L-Pen5]enkephalin.
April 1991, Molecular pharmacology,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Evidence for delta receptor mediation of [D-Pen2,D-Pen5]-enkephalin (DPDPE) analgesia in mice.
January 1986, NIDA research monograph,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Comparative binding properties of linear and cyclic delta-selective enkephalin analogues: [3H]-[D-Thr2, Leu5] enkephalyl-Thr6 and [3H]-[D-Pen2, D-Pen5] enkephalin.
April 1985, FEBS letters,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Development of delta-opioid receptors in rat brain characterised by [3H]-[D-Pen2,D-Pen5] enkephalin binding.
January 1986, NIDA research monograph,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Studies in vivo with ICI 174864 and [D-Pen2, D-Pen5]enkephalin.
February 1985, Neuropeptides,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Differences in the binding of [3H][D-Ser2,Thr6]leucine-enkephalin and [3H][D-Pen2,D-Pen5]enkephalin to brain membranes of morphine tolerant-dependent rats.
September 1991, European journal of pharmacology,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Binding of [3H][D-Ala2, MePhe4, Gly-ol5] enkephalin, [3H][D-Pen2, D-Pen5]enkephalin, and [3H]U-69,593 to airway and pulmonary tissues of normal and sensitized rats.
January 1997, Peptides,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides.
July 1996, International journal of peptide and protein research,
S J Weber, and D L Greene, and S D Sharma, and H I Yamamura, and T H Kramer, and T F Burks, and V J Hruby, and L B Hersh, and T P Davis
Chronic effect of [D-Pen2,D-Pen5]enkephalin on rat brain opioid receptors.
August 1991, European journal of pharmacology,
Copied contents to your clipboard!