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Ze-Hui Gong

Publications and source records attributed to Ze-Hui Gong.

4 recordsLinked to original sources
PubMed2007

Thienorphine: receptor binding and behavioral effects in rhesus monkeys.

Thienorphine is an oripavine with long-lasting antinociceptive effects in mice that are thought to be mediated by mu-opioid receptors. This study examined the receptor binding of thienorphine in cell membrane homogenates and its behavioral effects in rhesus monkeys (Macaca mulatta). Affinity and potency were determined using radioligand displacement and stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding in C6 (mu, delta) and Chinese hamster ovary (kappa) cell membranes. Thienorphine displayed high affinity for kappa-, mu-, and delta-opioid receptors with K(i) values of 0.14, 0.22, and 0.69 nM, respectively. Thienorphine partially stimulated kappa-opioid (75%) and mu-opioid (19%) receptors and not delta-opioid receptors. Thienorphine dose-dependently increased tail-withdrawal latency for 50 degrees C water and not 55 degrees C water with effects lasting for more than 7 days. The kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) (3.2 mg/kg) and a large dose (1.0 mg/kg) of naltrexone prevented thienorphine-induced antinociception. Thienorphine enhanced the antinociceptive effects of morphine and U50,488 [trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide] with 50 degrees C water; with 55 degrees C water, thienorphine enhanced the effects of morphine and attenuated the effects of U50,488. In other monkeys, thienorphine decreased responding in both components of a multiple schedule of food presentation and stimulus shock termination for up to 8 days; naltrexone and nor-BNI partially prevented these rate-decreasing effects. In morphine-treated monkeys discriminating naltrexone, thienorphine, and U50,488 neither substituted for nor modified the naltrexone discriminative stimulus. Thienorphine and U50,488 produced the same directly observable signs. These results show that thienorphine has long-lasting effects that seem to be mediated by low-efficacy agonism at kappa-opioid receptors, both in vitro and in vivo.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2006

Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction.

Analgesics, Opioid↗
PubMed2005

[Neurogenesis: a novel strategy for the treatment of depression].

It is now generally accepted that the birth of new neurons occurs in brain areas such as hippocampus throughout the lifespan. The waning and waxing of neurogenesis in hippocampus is proposed as a key factor in the decent into and recovery from depression. If hippocampal neurogenesis was blocked, antidepressant would lose its behavioral effects in behavioral models of depression. Long-term, but not short-term, treatment with different classes of antidepressant could stimulate neurogenesis in the hippocampus remarkably. As the regulation of adult neurogenesis continues to be identified, it will provide novel avenues of studying the mechanism and developing pharmacological agents for depressive disorder.

Animals↗