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Antinociceptive profile of biphalin, a dimeric enkephalin analog.
J Pharmacol Exp Ther. 1993 Jun; 265(3):1446-54.JP

Abstract

The dimeric enkephalin biphalin (Try-D-Ala-Gly-Phe-NH)2 was evaluated in mice using antinociceptive, gastrointestinal and physical dependence paradigms and compared with that of morphine (reference mu agonist) and etorphine (ultrapotent opioid agonist). Intracerebroventricular biphalin was 6.7- and 257-fold more potent than etorphine or morphine in eliciting antinociception. When administered i.t., biphalin produced only a 60% maximal antinociceptive effect in the tail-flick test even when given at doses up to 3 orders of magnitude higher than those effective i.c.v.; morphine was equipotent in this assay when given i.c.v. or i.t. Both morphine and biphalin were equipotent after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration, only a small fraction of [125I]biphalin was shown to penetrate to the brain (0.051 +/- 0.011%, at 20 min). After i.c.v. administration, biphalin antinociception was antagonized by receptor selective doses of beta-funaltrexamine (mu antagonist), naloxonazine (mu 1 antagonist), ICI 174,864 (delta antagonist) and [D-Ala2,Cys4]deltorphin (delta 2 antagonist), but not by [D-Ala2,Leu5,Cys6]enkephalin (delta 1 antagonist) or nor-binaltorphimine (kappa antagonist), whereas etorphine antinociception was significantly antagonized only by beta-funaltrexamine and naloxonazine. Intracerebroventricular biphalin inhibited gastrointestinal propulsion at doses 8-fold higher than those producing i.c.v. antinociception; i.c.v. morphine showed a similar antinociceptive and gastrointestinal propulsion A50. Intraperitoneal biphalin, but not i.p. morphine, showed little, if any, physical dependence, but both biphalin and morphine produced significant physical dependence when equiantinociceptive doses were infused i.c.v.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Pharmacology, University of Arizona, Tucson.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8389867

Citation

Horan, P J., et al. "Antinociceptive Profile of Biphalin, a Dimeric Enkephalin Analog." The Journal of Pharmacology and Experimental Therapeutics, vol. 265, no. 3, 1993, pp. 1446-54.
Horan PJ, Mattia A, Bilsky EJ, et al. Antinociceptive profile of biphalin, a dimeric enkephalin analog. J Pharmacol Exp Ther. 1993;265(3):1446-54.
Horan, P. J., Mattia, A., Bilsky, E. J., Weber, S., Davis, T. P., Yamamura, H. I., Malatynska, E., Appleyard, S. M., Slaninova, J., & Misicka, A. (1993). Antinociceptive profile of biphalin, a dimeric enkephalin analog. The Journal of Pharmacology and Experimental Therapeutics, 265(3), 1446-54.
Horan PJ, et al. Antinociceptive Profile of Biphalin, a Dimeric Enkephalin Analog. J Pharmacol Exp Ther. 1993;265(3):1446-54. PubMed PMID: 8389867.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antinociceptive profile of biphalin, a dimeric enkephalin analog. A1 - Horan,P J, AU - Mattia,A, AU - Bilsky,E J, AU - Weber,S, AU - Davis,T P, AU - Yamamura,H I, AU - Malatynska,E, AU - Appleyard,S M, AU - Slaninova,J, AU - Misicka,A, PY - 1993/6/1/pubmed PY - 1993/6/1/medline PY - 1993/6/1/entrez SP - 1446 EP - 54 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 265 IS - 3 N2 - The dimeric enkephalin biphalin (Try-D-Ala-Gly-Phe-NH)2 was evaluated in mice using antinociceptive, gastrointestinal and physical dependence paradigms and compared with that of morphine (reference mu agonist) and etorphine (ultrapotent opioid agonist). Intracerebroventricular biphalin was 6.7- and 257-fold more potent than etorphine or morphine in eliciting antinociception. When administered i.t., biphalin produced only a 60% maximal antinociceptive effect in the tail-flick test even when given at doses up to 3 orders of magnitude higher than those effective i.c.v.; morphine was equipotent in this assay when given i.c.v. or i.t. Both morphine and biphalin were equipotent after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration, only a small fraction of [125I]biphalin was shown to penetrate to the brain (0.051 +/- 0.011%, at 20 min). After i.c.v. administration, biphalin antinociception was antagonized by receptor selective doses of beta-funaltrexamine (mu antagonist), naloxonazine (mu 1 antagonist), ICI 174,864 (delta antagonist) and [D-Ala2,Cys4]deltorphin (delta 2 antagonist), but not by [D-Ala2,Leu5,Cys6]enkephalin (delta 1 antagonist) or nor-binaltorphimine (kappa antagonist), whereas etorphine antinociception was significantly antagonized only by beta-funaltrexamine and naloxonazine. Intracerebroventricular biphalin inhibited gastrointestinal propulsion at doses 8-fold higher than those producing i.c.v. antinociception; i.c.v. morphine showed a similar antinociceptive and gastrointestinal propulsion A50. Intraperitoneal biphalin, but not i.p. morphine, showed little, if any, physical dependence, but both biphalin and morphine produced significant physical dependence when equiantinociceptive doses were infused i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8389867/Antinociceptive_profile_of_biphalin_a_dimeric_enkephalin_analog_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8389867 DB - PRIME DP - Unbound Medicine ER -