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Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors.
J Pharmacol Exp Ther. 1987 Jan; 240(1):150-8.JP

Abstract

The tolerance effects of continuous intrathecal infusions of opioids at mu and delta receptors were studied in rats. These effects were compared to those of chronic systemic morphine. A chronic intrathecal infusion of the relatively selective delta agonist, [D-Ala2, D-Leu5]enkephalin (DADLE), produced a larger degree of tolerance to DADLE than to the highly specific mu-activating morphiceptin analog [N-methyl-Phe3, D-Pro4]morphiceptin (PL017). The slope of the analgesic dose-response curve for the highly specific delta agonist, cyclic [D-Penicillamine2, D-Penicillamine5]enkephalin (DPDPE), was significantly different (flatter) from those of mu agonists or DADLE. High-dose infusion of PL017 induced a 61-fold parallel shift of the dose-response curve for PL017. This same treatment also induced a corresponding flattened, nonparallel change of the dose-response curve for DADLE. This altered curve for DADLE was very similar in slope to that of DPDPE. Pretreatment with the irreversible mu antagonist, beta-funaltrexamine, caused a parallel rightward shift of the dose-response curve for PL017 but did not affect DPDPE activity. beta-Funaltrexamine treatment induced a nonparallel rightward shift of the dose-response curve for DADLE with a change of slope similar to that of DPDPE. These findings demonstrate a mixed mu-delta analgesic activity for the compound DADLE, which is often referred to as a prototypic delta agonist. These interactions differ from prior reports of none or minimal mu-ligand interactions with DADLE. Despite the cross-reactivity of DADLE to mu receptors, DADLE remains a more effective analgesic than do mu agonists in states of mu receptor tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors

Russell RD
No affiliation info available
Leslie JB
No affiliation info available
Su YF
No affiliation info available
Watkins WD
No affiliation info available
Chang KJ
No affiliation info available

MeSH

AnalgesiaAnimalsDose-Response Relationship, DrugDrug ToleranceEndorphinsEnkephalin, D-Penicillamine (2,5)-Enkephalin, LeucineEnkephalin, Leucine-2-AlanineEnkephalinsInjections, SpinalMaleMorphineNaloxoneNarcoticsRatsRats, Inbred StrainsReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, muSpinal Cord

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

3027302

Citation

Russell, R D., et al. "Continuous Intrathecal Opioid Analgesia: Tolerance and Cross-tolerance of Mu and Delta Spinal Opioid Receptors." The Journal of Pharmacology and Experimental Therapeutics, vol. 240, no. 1, 1987, pp. 150-8.
Russell RD, Leslie JB, Su YF, et al. Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors. J Pharmacol Exp Ther. 1987;240(1):150-8.
Russell, R. D., Leslie, J. B., Su, Y. F., Watkins, W. D., & Chang, K. J. (1987). Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors. The Journal of Pharmacology and Experimental Therapeutics, 240(1), 150-8.
Russell RD, et al. Continuous Intrathecal Opioid Analgesia: Tolerance and Cross-tolerance of Mu and Delta Spinal Opioid Receptors. J Pharmacol Exp Ther. 1987;240(1):150-8. PubMed PMID: 3027302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors. AU - Russell,R D, AU - Leslie,J B, AU - Su,Y F, AU - Watkins,W D, AU - Chang,K J, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 150 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 240 IS - 1 N2 - The tolerance effects of continuous intrathecal infusions of opioids at mu and delta receptors were studied in rats. These effects were compared to those of chronic systemic morphine. A chronic intrathecal infusion of the relatively selective delta agonist, [D-Ala2, D-Leu5]enkephalin (DADLE), produced a larger degree of tolerance to DADLE than to the highly specific mu-activating morphiceptin analog [N-methyl-Phe3, D-Pro4]morphiceptin (PL017). The slope of the analgesic dose-response curve for the highly specific delta agonist, cyclic [D-Penicillamine2, D-Penicillamine5]enkephalin (DPDPE), was significantly different (flatter) from those of mu agonists or DADLE. High-dose infusion of PL017 induced a 61-fold parallel shift of the dose-response curve for PL017. This same treatment also induced a corresponding flattened, nonparallel change of the dose-response curve for DADLE. This altered curve for DADLE was very similar in slope to that of DPDPE. Pretreatment with the irreversible mu antagonist, beta-funaltrexamine, caused a parallel rightward shift of the dose-response curve for PL017 but did not affect DPDPE activity. beta-Funaltrexamine treatment induced a nonparallel rightward shift of the dose-response curve for DADLE with a change of slope similar to that of DPDPE. These findings demonstrate a mixed mu-delta analgesic activity for the compound DADLE, which is often referred to as a prototypic delta agonist. These interactions differ from prior reports of none or minimal mu-ligand interactions with DADLE. Despite the cross-reactivity of DADLE to mu receptors, DADLE remains a more effective analgesic than do mu agonists in states of mu receptor tolerance.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/3027302/Continuous_intrathecal_opioid_analgesia:_tolerance_and_cross_tolerance_of_mu_and_delta_spinal_opioid_receptors_ DB - PRIME DP - Unbound Medicine ER -