Differential right shifts in the dose-response curve for intrathecal morphine and sufentanil as a function of stimulus intensity
1995; Lippincott Williams & Wilkins; Volume: 62; Issue: 3 Linguagem: Inglês
10.1016/0304-3959(95)00006-e
ISSN1872-6623
AutoresDavid M. Dirig, Tony L. Yaksh,
Tópico(s)Neurotransmitter Receptor Influence on Behavior
ResumoTo assess effects of stimulus intensity, dose-response curves in rats for radiant heat-evoked withdrawal of the hind paw was assessed after the intrathecal (i.t.) injection of sufentanil and morphine, mu-opioid agonists differing in intrinsic activity, at Low, Medium, and High stimulus intensities. Baseline latencies observed at the 3 intensities were: low = 14.5 ± 0.3; medium = 8.9 ± 0.2; high = 5.7 ± 0.1 sec. After i.t. administration of sufentanil or morphine, there was a dose-dependent, naloxone-reversible elevation in nociceptive threshold. With increased stimulus intensity, there was a right shift in the dose-response curves with morphine exhibiting a greater magnitude right shift than that of sufentanil. Dose ratios (ED50 Medium/ED50 Low and ED50 High/ED50 Low) with 95% CI for sufentanil were, respectively, 2.5 (2.2–2.9) and 7.7 (6.7–8.9), and the dose ratio for morphine (ED50 Medium/ED50 Low) was 34 (28–41). At the highest intensity, due to a plateau in the morphine dose-response curve, ED50 and dose ratio calculations could not be performed. The present study supports the pharmacological model of receptor occupany, such that the higher efficacy receptor agonist, sufentanil, demonstrated a lesser magnitude right shift than the lower efficacy agonist, morphine, while at the high stimulus intensity, morphine but not sufentanil, was a partial agonist.
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