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Aim: To study the mechanism of dihydroetorphine (DHE) tolerance., Methods: DHE tolerance was produced by repeated s.c. injections in progressively increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP-HPLC/fluorescence assay and radioimmunoassay, respectively., Results: The basal contents of glutamic acid (Glu), aspartic acid (Asp), and GABA in whole brain (cerebellum removed) were increased respectively from 14.1 +/- 2.1, 3.0 +/- 0.4, and 1.8 +/- 0.8 mumol/g tissue in control mice to 17.2 +/- 2.2, 4.1 +/- 0.6, and 3.2 +/- 1.0 mumol/g tissue in tolerant mice, and the rates of increase were 22.0% (P < 0.05), 36.7% (P < 0.01), and 77.8% (P < 0.05 vs control), respectively. There was no significant difference in the basal contents of Gln (5.1 +/- 1.0 vs 4.5 +/- 1.7 mumol/g tissue of control). The basal contents of cAMP in hypothalamus and striatum were decreased respectively from 271 +/- 38 and 189 +/- 31 nmol/g tissue in control mice to 96 +/- 15 and 65 +/- 21 nmol/g tissue in tolerant mice (P < 0.01), and the rates of decrease were 64.6% and 65.6%, respectively. There was no significant difference of cAMP in cerebral cortex (72 +/- 20 vs 55 +/- 15 nmol/g tissue of control)., Conclusion: The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.

Objective: To determine the effect of dihydroetorphini hydrochloride (DHE) on parturition of mice., Methods: 180 pregnant mice were divided equally into 6 groups. DHE was administered intramuscularly (i.m.) to mice group A, B and C at the dose levels of 1, 2 and 4 micrograms/kg respectively. Morphine hydrochloride 200 micrograms/kg (hypodermic) was given to group D and procaine hydrochloride 1000 micrograms/kg i.m. for group E, while for group F as control distilled water was given. Each preparation was given to the pregnant mice 3 times, i.e. 18 hours before the date of confinement, during labor and 2 hours postpartum., Results: No effects on mice parturition were found in group A, B, E, and F. The percentage of cyanosis in newborn mice of group C and D was 13.8% and 22.8% respectively, which was significantly higher than that (7.4%) in group F., Conclusion: DHE is safer than morphine and procaine for analgesia during labor, and no adverse effects of DHE at dose levels of 1 microgram/kg and 2 micrograms/kg were observed on mice parturition.

Dihydroetorphine (DHE) inhibited contraction response of isolated guinea pig ileum and mouse vas deferens induced by electric field stimulation with IC50 values of (4.4 +/- 4.3) x 10(-16) mol.L-1 and (1.1 +/- 1.4) x 10(-18) mol.L-1 respectively. These effects of DHE were antagonized by naloxone (Nal). On guinea pig ileum, the antagonistic effect of Nal against DHE was similar to those against morphine and etorphine. However, on mouse vas deferens, the antagonistic effect of Nal against DHE was more potent than those against morphine and etorphine. Besides, DHE showed antagonistic effect on k-receptors in isolated rabbit vas deferens.