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Dopamine receptor antagonist and application thereof

A receptor antagonist and dopamine technology, applied in the field of isoquinoline alkaloids, can solve the problems of unpredictable d-tetrahydrojatrorrhizine antagonistic effect and analgesic effect, etc. The effect of ion influx

Active Publication Date: 2020-05-22
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, it is impossible to predict that d-tetrahydrojatrorrhizine has dopamine receptor antagonism and analgesic effects from the existing research.

Method used

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  • Dopamine receptor antagonist and application thereof
  • Dopamine receptor antagonist and application thereof
  • Dopamine receptor antagonist and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] Example 1: Detection of changes in calcium flow of d-tetrahydrojatrorrhizine in cells stably expressing dopamine receptor D1 or D2: evaluation of the receptor activity of d-tetrahydrojatrorrhizine at the cellular level.

[0039] On HEK-293 cells stably expressing dopamine receptor D1 or D2, the effect of d-tetrahydrojatrorrhizine on dopamine-induced calcium ion influx was detected. HEK-293 cells stably expressing dopamine receptor D1 or D2 (purchased from the Cell Bank of Chinese Academy of Sciences) were mixed with 4×10 4 Each well was spread in a 96-well plate. After the cells adhered to the wall, each well was washed twice with PBS, and 100 μl of calcium flow reagent (purchased from Molecular Devices) was added to each well for 50 minutes, and then different concentrations of d-tetrahydro Jatrorrhizine continued to incubate for 10 minutes. After incubation, dopamine was added to stimulate and the change of calcium flow was detected immediately with a microplate reader ...

Embodiment 2

[0040] Example 2: Study on the analgesic effect of intraperitoneal injection of d-tetrahydrojatrorrhizine in mouse hot plate experiment: evaluate the analgesic effect of the compound of the present invention on acute pain.

[0041] The C57 male mice of 6-8 weeks were divided into five groups, respectively control group, morphine treatment group (Morphine) and d-tetrahydrojatrorrhizine (5mg / kg, 10mg / kg, 20mg / kg) treatment group ( CPM-5mg / kg, CPM-10mg / kg, CPM-20mg / kg), 6-8 mice in each group. Before the start of the experiment, the mice were first trained for three days, and the temperature of the hot plate was adjusted so that the pain-inducing latency of the mice to the hot plate was between 6-8 seconds. During the formal experiment, the temperature of the hot plate was adjusted to 54°C, and the baseline was recorded. After the intraperitoneal injection of the drug, the pain-inducing latency time of the mice was detected at 30, 60, 120, and 180 min, respectively. Experimenta...

Embodiment 3

[0042] Example 3: Study on the analgesic effect of intraperitoneal injection of d-tetrahydrojatrorrhizine in a mouse model of inflammatory pain induced by CFA: the analgesic effect of the compound of the present invention on inflammatory pain was evaluated.

[0043] The C57 male mice of 6-8 weeks were divided into three groups, respectively control group, morphine treatment group (Morphine) and d-tetrahydrojatrorrhizine (20mg / kg) treatment group (CPM-20mg / kg), each Group 6-8 mice. The mice were placed in the device 3 days in advance to measure the baseline of mechanical pain threshold and heat radiation paw withdrawal latency, and the model was established on the third day. When the model was established, 20 μl of complete Freund's adjuvant was injected into the sole of the right foot of each mouse with a microinjector, and administered one day after the model was established. Before administration and 1 hour, 2 hours, and 3 hours after administration, the mechanical pain thr...

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Abstract

The invention discloses a dopamine receptor antagonist and an application thereof. The dopamine receptor antagonist includes 2,9,10-trimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinolin-3-ol and a pharmaceutically acceptable salt or precursor compound. The dopamine receptor antagonist can antagonize a calcium influx caused by activation of a dopamine receptor, widen the application range of analgesia for a ligand of the dopamine receptor, and find a novel idea for development of a novel drug. Animal experiments provided by the invention prove that the 2,9,10-trimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinolin-3-ol has a good analgesic effect on acute pain, inflammatory pain and bone cancer pain as the dopamine receptor antagonist.

Description

technical field [0001] The present invention belongs to the technical field of medicine, and specifically relates to a dopamine receptor antagonist and its application, in particular to an isoquinoline alkaloid with analgesic effect. It exerts analgesic effect by antagonizing dopamine D2 receptors. Background technique [0002] Pain is an unpleasant sensory and emotional experience resulting from tissue damage or potential tissue damage. There are many ways to classify pain, according to the duration of pain can be divided into acute pain and chronic pain. Acute pain is usually due to tissue damage, such as skin burns and fractures. This type of pain usually goes away as the wound heals and the stimulus that caused the pain is eliminated. Chronic pain refers to persistent pain after wound healing, cancer pain, persistent or degenerative disease-related pain, and long-term pain caused by unknown causes, including neuropathic pain, visceral pain, cancer pain, inflammatory p...

Claims

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Application Information

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IPC IPC(8): A61K31/4375A61K36/66A61P29/00A61P25/00A61P35/00A61P25/18A61P25/14A61P25/16A61P25/30
CPCA61K31/4375A61K36/66A61P29/00A61P25/00A61P35/00A61P25/18A61P25/14A61P25/16A61P25/30
Inventor 张岩邱鑫范超
Owner SHANGHAI JIAO TONG UNIV
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