Use of beta-adrenergic receptor biased antagonists in pharmacy
A technology of adrenaline and antagonists, applied in the field of β-adrenergic receptor biased antagonists in pharmaceuticals, β-adrenergic receptor biased antagonists, can solve problems such as memory overstrengthening, unclear, memory loss, etc., to achieve Effect of reducing side effects of the nervous system, high safety factor, and small side effects
Active Publication Date: 2020-07-10
FUDAN UNIV
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Problems solved by technology
In 2000, Nader et al again proposed and proved that the destruction of memory reconsolidation will lead to memory loss or memory overstrengthening
However, the physiological function of the activation of a large number of β-arrestin biased signaling pathways is still unclear, especially whether it plays a role in the nervous system is completely unclear
In view of our previous research, we found that β-arrestin2 participates in the formation of conditioned fear memory consolidation and the long-term enhancement of amygdala synaptic plasticity through the strict negative regulation of PKA activity; and the regulation of β-arrestin2 on learning and memory and impact are still far from clear; more importantly, the role of biased antagonists in learning and memory has not yet been studied; based on previous research results, the inventors of the present application intend to provide β-adrenoreceptor biased antagonists in preparation The new application in , so as to further provide drug targets for clinical treatment of senile dementia and prevention of post-traumatic stress syndrome
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Embodiment 1
[0042] 1. Experimental materials and methods
[0043] 1.1 Experimental animals and grouping
[0044] Clean-grade adult male C57 / BL6 mice (provided by the Animal Center of the Chinese Academy of Sciences), 8-10 weeks old, 25-28g, the animals were raised in the animal room of the laboratory for 2-3 days before operation, free to eat and drink, room temperature 20-22°C, The humidity was 55±5%, and the day and night were reversed for 12 hours. The experiment began after the animals acclimated to the environment for a week. The mice were randomly divided into control group, carvedilol group (10 μg / mouse, intracerebroventricular administration), alprenolol group (10 μg / mouse, intracerebroventricular administration), propranolol (10 mg / kg, intraperitoneal injection) and betaxolol (1mg / kg, intraperitoneal injection), 11-18 rats in each group were tested for memory ability.
[0045] 1.2 Model preparation
[0046] Object discrimination behavioral model: Object discrimination behavior...
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The invention relates to the field of central nervous system drugs, and particularly relates to an application of beta- adrenocepter biased antagonists in pharmacy. In particular, the invention relates to the application of the beta-adrenocepter biased antagonists carvedilol and alprenolol in preparing a drug for promoting a central nervous system to learn memory. Through two different mice memory model tests of new object recognition and conditioned fear memory, results confirm that the beta-adrenocepter biased antagonist carvedilol or alprenolol can improve reconsolidation of the mice conditioned fear memory and has no significant effect on reconsolidation of the new object recognition memory, and the beta-adrenocepter non-biased antagonists such as propranolol and betaxolol can suppress reconsolidation of the mice conditioned fear memory and the object recognition memory. The beta-adrenocepter biased antagonists can be used for preparing the drug for promoting the central nervous system to learn memory.
Description
technical field [0001] The invention relates to the field of central nervous system drugs, and relates to the use of a beta-adrenoreceptor biased antagonist in pharmacy. In particular, it relates to the use of β-adrenergic receptor biased antagonists (such as carvedilol: carvedilol and alprenolol) in the preparation of drugs for promoting learning and memory in the central nervous system. Background technique [0002] The current research on memory, one of the advanced functions of the brain, is a frontier hotspot in the field of neuroscience, and it is also one of the 25 major problems in the field of natural science today, especially for the study of how the nervous system responsible for learning and memory stores and manages a large amount of information from the outside world has been an important challenge in neuroscience. Therefore, research on all levels of memory is particularly important for understanding the pathogenesis and clinical treatment of neurological and...
Claims
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IPC IPC(8): A61K45/00A61K31/403A61K31/138A61P25/00A61P25/28
Inventor马兰刘星黄冰陶冶铮
OwnerFUDAN UNIV