CN108785304A - A kind of application of ampa receptor agonist - Google Patents
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- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
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Abstract
The invention discloses a kind of application of ampa receptor agonist, the ampa receptor agonist is PF-4778574, and structural formula is：；Molecular formula is：C19H22N2O3S2;Compound molecular weight is 390.52;The PF-4778574 is applied in quick antidepressant.Its purposes in preparing quick antidepressant belongs to first public, and it is curative for effect, side effect is low.
Description
Technical field
The present invention relates to pharmaceutical technology field, more particularly to a kind of application of ampa receptor agonist.
Background technology
Depression is a kind of mental disease showed by psychology, behavior and physiological signs, including depressive emotion, note
Power of anticipating declines, the change of appetite and sleep pattern, hebetude, anhedonia in various activities, unworthy feeling, excessively
Feeling of guilt even commit suiside.With modern society's intensified competition, the development of economic fast transformation, cause the hair of depression in recent years
Sick rate constantly rises.Depression generally existing in life at present may occur in the stage of life very early.According to international pre- preventing
(the true and data) display in 2015 of guilty association, the suicide risk of depression is higher, occurs every about 40 seconds primary Suicide dead
Die event.The lifetime prevalence of Major Depressive Disorder is 15% to 20%, and high recurrence rate is up to 30% to 40% and may develop into refractory
Depression of sex.The statistical forecast of the World Health Organization (WHO)：The second largest reason that the disease that the year two thousand twenty leads to disables will likely be suppression
Strongly fragrant disease.
The pathophysiological mechanism for the antidepressant clinically widely applied at present is by increasing synaptic cleft monoamine
The level of class mediator.Unfortunately, conventional antidepressants such as selective serotonin reuptake inhibitor (Selective
Serotonin Reuptake Inhibitors, SSRIs) only there is appropriate therapeutic effect and remission rate and with unnecessary
Side effect, SSRIs, which works, in addition usually requires 3-8 week time, this is particularly hazardous to the high patient of risk that commits suiside.Therefore,
There is an urgent need to develop effective, snap action antidepressants.The reason of antidepressants action delay may be to need an increasing
The adaptation process of strong neural plasticity and cell elasticity.Clinical and preclinical study shows the dysfunction of glutamatergic system
It is related to mental handicape, such as Major Depressive Disorder and Bipolar Depression.The serum glutaminic acid level of patients with depression is higher than non-depressed trouble
The severity of person, plasma glutamate levels and patients who suffered with depression has stringent positive correlation and raised in anti depressant therapy
Glutamate levels can reduce, these results promote the conditioning agent for glutamic acid system to be developed.Research finds low dose
Measure the uncompetitive blockade agent of N-methyl-D-aspartate (N-methyl-D-aspartic acid, NMDA) receptor
Ketamine has quick antidepressant effect.The Ketamine of single dose upon administration 2 hours generate antidepressant effect, and
The antidepression duration is up to 7 days in clinical (MDD patient) and preclinical depression model.Its mechanism of action shows Ketamine
Quick antidepressant effect is played by raising BDNF levels and activation mTOR signal paths.And find that ampa receptor excitement is anti-at it
It plays primary in depressed mechanism and must act on.In addition it has been proved to be able to activate BDNF/TrkB/ after ampa receptor activation
MTORC1 signal paths then increase the expression such as GluR1, PSD-95 and Synapsin I and inside forehead of synapsin
The excitatory synapse of leaves layer (mPFC) transmits.These research shows that Ketamine quickly antidepressant important molecule access may
It is to activate ampa receptor by TrkB/PI3K/AKT/mTORC1 signal transduction pathways to mediate the release of BDNF.In addition neural
Peptide VGF also assisted in C-terminal peptide TLQP-62 antidepressions effect of the quick antidepressant effect of ketamine and neuropeptide VGF also according to
Rely in the activation of ampa receptor and the conduction of mTOR signals.The quick anti-suppression of nmda receptor Glycine site agonist GLYX-13
Yu Zuoyong is also related to PI3K/AKT/mTORC1/VGF signal transduction pathways.And Vgf gene deregulations significantly block in hippocampus
The quick antidepressant effect of GLYX-13 has simultaneously blocked GLYX-13 to make the regulation and control of PI3K/AKT/mTORC1 signal transduction pathways
With further demonstrate VGF and BDNF has in the quick antidepressant effect of regulation and control PI3K/AKT/mTORC1 signal paths participation
Similar mechanism of action can be shown that BDNF and VGF upstream regulatory mechanisms having the same in participating in quick antidepression.And have
Report shows that the antidepressant effect of GLYX-13 also relies on the activation of ampa receptor, may confirm ampa receptor as BDNF and
The common regulation and control target of VGF, participates in quick antidepression process.
Ampa receptor is central excitatory ionotropic glutamate receptor, is made of four kinds of core subunit GluR1-4, is mediated
Central nervous system signal conducts, and promotes neurodevelopment and synaptic plasticity, participates in a variety of nervous activity processes.And in 2015
It is considered as innovation chemical medicine field that the scientific and technological key special subjects of degree national " great new drug initiative ", which are declared in guide, to pay close attention to
One kind with the relevant important target spot of Neuropsychic diseases.Ketamine as previously described due to its quick antidepressant effect and
Extensive concern is caused, Unfortunately, the spirit of Ketamine is heterogeneous, and abuse risk and other side effects limit it
Extensive clinical application.Therefore exploitation with Ketamine similar to antidepressant effect but the less compound of side effect is with important
Meaning.Ampa receptor forward direction allosteric modulators are excellent with relatively low neurotoxicity due to its mild exciting ampa receptor in recent years
Gesture becomes the hot spot for the treatment of neuropsychiatric disease medicament research and development.Cortex drugmakers of the U.S., Organon companies of Holland, France
The ampa receptor forward direction allosteric tune that Servier companies, Lilly companies and Glaxo Smith Kline companies have developed at present
It saves in agent, is in preclinical study stage or clinical experimental stage mostly, pharmacotoxicological effect is focused primarily upon to cerebral injury
Neuroprotection and improve cognition effect, and about the novel positive allosteric modulators regulation and control behavior depression of ampa receptor and
Its mechanism illustrates far away.
PF-4778574 is a kind of new A MPA receptor stimulating agents, can by simultaneously mitigate ampa receptor inactivation and desensitize with
Enhancing and extend synaptic currents come come enhance ampa receptor activity, be a kind of new A MPA receptors forward direction allosteric modulators, and join
With the development for adjusting nerve cell, improve cognition.But can PF-4778574 antidepression and its antidepressant dosage and be
It is no that there is quick antidepressant function to be found for the first time by us.
Invention content
The technical problem to be solved by the invention for the present situation of prior art is to provide new A MPA receptor stimulating agents
Applications of the PF-4778574 in quick antidepressant, it is curative for effect, side effect is low.
Technical solution is used by the present invention solves above-mentioned technical problem：
A kind of application of ampa receptor agonist, ampa receptor agonist are PF-4778574, and structural formula is：
；
Molecular formula is：C19H22N2O3S2;Compound molecular weight is 390.52;Chemical name：N-[(3R,4S)-3-[4-(5-
Cyano-2-thienyl)phenyl]tetrahydro-2H-pyran-4-yl]-2-propanesulfonamide N-{(3R,
4S)-3-[4-(5-Cyano-2-thienyl)phenyl]tetrahydro-2H-pyran-4-yl}propane-2-
sulfonamide;PF-4778574 is applied in quick antidepressant.
To optimize above-mentioned technical proposal, the concrete measure taken further includes：
In above-mentioned quick antidepressant, the dosage of PF-4778574 is 1mg/kg or 2mg/kg.
Include PF-4778574 compounds or its drug acceptable salt in above-mentioned quick antidepressant.
The administering mode of above-mentioned quick antidepressant is ejection preparation, oral preparation or external preparation.
The dosage form of above-mentioned quick antidepressant includes tablet, capsule, powder, pill, granule, injection
Or emulsion.
Compared with prior art, ampa receptor agonist PF-4778574 of the invention is applied to quick antidepressant
In, the purposes in preparing quick antidepressant belongs to first public, and it is curative for effect, side effect is low.
Description of the drawings
Fig. 1 PF-4778574 intervenes processing and Behavior test experiment flow figure；
The quick antidepressant effect experiment flow figures of Fig. 2 PF-4778574；
Fig. 3 ampa receptors are in the quick antidepressant effect experiment flow figures of PF-4778574；
The quick depressed sample action diagrams of Fig. 4 PF-4778574；
After Fig. 5 PF-4778574 single-doses, antidepressant effect time-effect relationship figure；
To the influence diagram of mouse Behavioral change after Fig. 6 PF-4778574 single-doses；
The quick antidepressant effect figures of Fig. 7 ampa receptor Antagonist blocks PF-4778574.
Specific implementation mode
Below in conjunction with attached drawing embodiment, present invention is further described in detail.
A kind of application of ampa receptor agonist, ampa receptor agonist are PF-4778574, and structural formula is：
；
Molecular formula is：C19H22N2O3S2;Compound molecular weight is 390.52;Chemical name：N-[(3R,4S)-3-[4-(5-
Cyano-2-thienyl)phenyl]tetrahydro-2H-pyran-4-yl]-2-propanesulfonamide N-{(3R,
4S)-3-[4-(5-Cyano-2-thienyl)phenyl]tetrahydro-2H-pyran-4-yl}propane-2-
sulfonamide;PF-4778574 is applied in quick antidepressant.
In embodiment, in quick antidepressant, the dosage of PF-4778574 is 1mg/kg or 2mg/kg.
Include PF-4778574 compounds or its drug acceptable salt in embodiment, in quick antidepressant.
In embodiment, the administering mode of quick antidepressant is ejection preparation, oral preparation or external preparation.
In embodiment, the dosage form of quick antidepressant includes tablet, capsule, powder, pill, granule, note
Penetrate agent or emulsion.
Effects of the ampa receptor agonist PF-4778574 in quick anti-depression aspect is confirmed below by experiment.
1. experimental animal
Animal needed for experiment is all from Zhejiang Medical research institute animal center, strain ICR, male, weight 22-25g.
In the SPF grade animal houses raising that University Of Ningbo's Experimental Animal Center provides, animal house temperature is controlled respectively with humidity at 22 ± 2 DEG C
With 60% ± 5%.The circadian rhythm 12 hours dark of illumination in 12 hours are controlled using fluorescent lamp, animal packet sub-cage rearing is given clear
Clean water, pellet are fed.It requires to carry out in particular room in strict accordance with experimental implementation, and abides by《Zhejiang Province's experimental animal pipe
Reason method》Provide and obtain the agreement of the animal welfare committee of medical college of University Of Ningbo.
2 Behaviors survey methods：
2.1 chronic unpredictable sexual stimulus (Chronic Unpredictable Stress, CUS) modelings
11 kinds of stimulations are used altogether：Fasting is prohibited water, is overturned round the clock, moist bedding and padding, fetters, and strobe light adds noise, shakes mouse cage, inclines
Oblique mouse cage, cold-wate swimming (10 DEG C), vola of shocking by electricity, hot water swim (40 DEG C).It is small that each stimulation is applied to CUS models at random daily
Mouse.
2.2 Naoliqing capsules, ventricles of the brain pipe laying and hippocampus micro-injection operation
Before experiment desktop and disinfection of surgical equipment are wiped with 75% medicinal alcohol.Mouse is taken out from mice rearing cage and is weighed.
2% Nembutal sodium solution gives corresponding Nembutal sodium solution body according to the dosage of 70mg/kg according to mouse actual weight
Product, intraperitoneal administration.About after five minutes, rat-tail is gently pinched without significant reaction, shows that mouse enters deep layer narcosis, you can start real
It tests.Mouse is fixed on stereotaxic apparatus fixator, pays attention to the balance for adjusting both sides ear bar, shakes mouse body with mouse
Head still is fixed Success criteria, then loads onto nose clip and fixes mouse front tooth.After the completion of fixation, first smeared in mice eye red
Mycin eye ointment removes mouse head hair to keep mice eye to moisten, with scissors, and scissors is stitched with other one in then and is cut
Mouse head skin is opened, exposure skull is wiped the connective tissue on surface layer with cotton swab.Open digital display Naoliqing capsule on desktop
Instrument display and micro-injection pump controller, upper lift micro-injection pump, fixed micro syringe.With reference to mouse brain map, before fixed
Fontanel, mobile syringe is to bregma, using bregma as zero, by desktop digital display instrument X-axis, Y-axis, Z axis zero.With reference to mouse brain map knot
Brain area needed for experiment, mobile syringe to corresponding position are closed, label is punched with cranial drill.Parameter needed for this experiment is：Side
Ventricles of the brain pipe laying, parameter are：AP：- 0.34 mm, ML：± 1.00mm, DV：-2.5 mm.The AAV viruses of intradermal injection VGLUT1, ginseng
Number is：AP：+ 1.78 mm, ML：± 0.30 mm, DV：-1.25 mm.The subsequent step of pipe laying is mouse after the completion of having punched
Brain is inserted into conduit, is fixed later with dental cement closing surrounding catheter, the mouse after dental cement is solidified is from fixer
It takes off and puts back to cage, give one week recovery time, micro syringe is then used to import drug in mouse brain by conduit,
Cortex virus injection is then directly injected by micro syringe in mouse brain, and injection time is 5 minutes, stops needle 3 minutes.
2.3 spacious fields test (Open filed test, OFT)
Spacious field device is 50 centimetres one long, and 50 centimetres wide, high 30 centimetres of square opens case, and entire babinet is white plastic material
Matter, spacious case different parts need uniform light when testing, bottom bottom are divided into four regions, setting-out trace with marking pen
Must not be too apparent, to prevent influencing the behavior of mouse.2 meters of place's suspension video cameras monitor in real time and record a video for dividing right over babinet
Analyse data.When test, mouse is put into from bottom of box middle, is recorded a video 5 minutes.Data record：(mouse is in case for standing number
When freely movable in son, forelimb leaves bottom only hind leg and lands, then it is primary to be denoted as standing)；Thread number (mouse freely activity
When, the number of each region is passed through, if passing through diagonal zones is then denoted as threading twice, adjacent area, which passes through, is denoted as threading one
It is secondary).10% alcohol wipe babinet, elimination smell mouse to prevent under the influence of are used after the test of every mouse.
2.4 forced swim tests (Forced Swimming Test, FST)
Experimental provision is 18 centimetres of a diameter, high 24 centimetres of transparent organic plastics drum, 15 centimetres of the depth of water, water temperature control
At 23 ± 2 DEG C.It tests in total 6 minutes, first two minutes are adaptation process, the four minutes mouse dead time after record.Mouse is motionless
Definition be：Mouse head-up swims in the water surface or does necessary small size travelling to keep head to keep afloat, such as unilateral
Hind leg stroke.The water with mouse is dried with towel after experiment and puts back to cage again.
2.5 syrup preferences test (Sucrose Preference Test, SPT)
The experiment of syrup preference is divided into two parts：It adapts to and tests.It adapts to share 72 hours.Adapt to two bottle 1% within wherein first 24 hours
Sucrose solution, then 24 hours adapt to one bottle of tap water, one bottle of 1% syrup, position is random, following 24 hours by previous bottle
The location swap of one bottle of 1% syrup of tap water, eliminates the position preference of mouse.It is small to prohibit water 24 later for free diet during adaptation
When, then a sugared water starts to test, and 24 hours testing times, records syrup, the consumption of tap water calculates syrup preference
Rate：(syrup consumption/total flow) × 100%.
2.6 new environment food rcstrictions test (Novelty Suppressed Feeding Test, NSFT)
Experimental provision is to utilize spacious field device, but by four wall blackings.Animal pretreatment is fasting 24 hours before testing, and drinking-water is certainly
By.When experiment, a food is placed in bottom center, and animal is put at any one angle of chest, video observation 5 minutes, calculate by
It is put into mouse to start to bite to mouse time of laboratory rodent chow, is incubation period (latency).Preclinical long short reaction is small
The Degree of Depression of mouse.After 5 minutes, mouse is put into transition cage, there is quantitative food, record mouse 5 minutes in cage
Interior food consumption quantity, to exclude appetite difference to preclinical influence.With the alcohol wipe of 10 % after the completion of every mouse experiment
Babinet eliminates smell mouse to prevent under the influence of.
Experiment 1：Whether there is the research of quick antidepressant effect about PF-4778574.
Bull ICR mouse 50 are only divided into 5 groups, every group 10, respectively Vehicle groups, CUS+Vehicle,
CUS+PF-4778574 (0.5mg/kg), CUS+PF-4778574 (1mg/kg), CUS+PF-4778574 (2mg/kg).Model is adopted
The corresponding drug of each group is given in a single dose after model construction success with classical CUS model constructions, spacious field is used after 24 hours
It tests, food rcstriction is tested under new environment, and syrup preference experiment, the behaviouristics method such as forced swim test detects PF-4778574
Whether there is quick antidepressant effect, and the variation for taking brain tissue to carry out protein molecular level detection related pathways albumen, it is real
It tests detailed process and sees Fig. 1.
To confirm PF-4778574 quickly antidepressant effects, we are by a large amount of preliminary experiment screening selection PF- early period
4778574 0.5 mg/kg, 1 mg/kg, the verification of 2 mg/kg Three doses play fast in the CUS depression models that success is built
Fast antidepressant effect.After model construction five weeks, threading number (Fig. 4 A, P in the experiment of CUS group mouse spacious fields<0.01) it and stands
Number (Fig. 4 B, P<0.01) conspicuousness is reduced compared with Vehicle groups；And dead time (Fig. 4 C, P in forced swimming
<0.01) and in food rcstriction experiment ingest incubation period (Fig. 4 E, P<0.01) it is significantly higher than Vehicle groups；Compared to
Vehicle groups, CUS group mouse pleasant sensations obviously lack (Fig. 4 D, P<0.01) after, showing CUS modelings five weeks, mouse obviously occurs
Depressive symptom, modeling success.It is dose-dependent anti-to show that PF-4778574 has for behaviouristics result after single-dose 24 hours
Depression effect.1 mg/kg of PF-4778574,2 mg/kg dosage significantly increase mouse in spacious field experiment compared with CUS groups
Threading number (Fig. 4 A, P<And standing number (Fig. 4 B, P 0.01)< 0.01)；In forced swim test, with CUS group phases
Than 1 mg/kg of PF-4778574,2 mg/kg dosage conspicuousnesses reduce dead time (Fig. 4 C, P of mouse< 0.01).Sugar
Water preference experiment in, 1 mg/kg of PF-4778574,2 mg/kg dosage syrup preference rate ratio CUS group conspicuousnesses increase (Fig. 4 D,
P < 0.01)；In food rcstriction experiment, mouse ingests 1 mg/kg, the 2 mg/kg dose ratios CUS of incubation period PF-4778574
Group significantly shortens (Fig. 4 E, P< 0.01).1 mg/kg, the 2 mg/kg dosage of behaviouristics result prompt PF-4778574 may have
Play the role of quickly improving mouse behavior depression.
Experiment 2：About the quick antidepression timeliness Journal of Sex Research of PF-4778574 single-doses.
Bull ICR mouse 40 are only equally divided into four groups：Vehicle, PF-4778574 (0.5 mg/kg), PF-
4778574 (1 mg/kg), PF-4778574 (2 mg/kg).First day (after administration 24 hours) after single-dose, the 4th day,
7th day, the tenth day four time points carried out spacious field experiment and forced swim test, and experiment detailed process is shown in Fig. 2.
Experiment 1, which has proven to PF-4778574, has quick antidepressant effect, and four have been selected about its antidepression duration
A time point goes to detect, and is respectively：First day (being equivalent to after administration 24 hours), the 4th day, the 7th day, the tenth day.Spacious field is real
Test threading number (Fig. 5 A, P of mouse>0.05) with standing number (Fig. 5 B, P>0.05) as being incremented by for number of days has slightly
Reduction, may be more with testing time, mouse adapt to environment it is related, there was no significant difference between each group.Mouse is in forced swimming
In dead time tested at first day find PF-4778574 1 mg/kg, 2 mg/kg dosage antidepressant effects it is the most notable
(Fig. 5 C, P<0.05, P< 0.01).Antidepressant effect is continued until the 7th day (Fig. 5 C, P<0.05, P<0.05), exist
1 mg/kg of tenth day PF-4778574,2 mg/kg dosage groups and Vehicle groups there was no significant difference (Fig. 5 C, P>
0.05), antidepressant effect disappears.Show that 1 mg/kg of single-dose PF-4778574,2 mg/kg dosage antidepressant effects can
It is for 1 week.
PF-4778574 significantly increases the standing number (figure in the experiment of CUS group spacious fields when playing quick antidepressant effect
4B, P<0.01) with threading number (Fig. 4 A, P<0.01), then whether PF-4778574 antidepressant effects change certainly with it
Main mobility is related.Single-dose carries out spacious field experiment and forced swim test after 24 hours.1 mg/ of PF-4778574
Kg, 2 mg/kg dosage group forced swimmings dead time be substantially less than Vehicle groups (Fig. 6 A, P<0.05, P<0.01),
Prompt has antidepressant effect.But there was no significant difference between the standing number of mouse and threading number each group in spacious field experiment
(Fig. 6 B, P> 0.05).Illustrate that PF-4778574 antidepressant effects are unrelated with the change of its autonomic activities ability.
Experiment 3：The research acted on during PF-4778574 quick antidepressions about ampa receptor.
Bull ICR mouse 40 only all carry out telocoele pipe laying, and parameter is：AP：- 0.34 mm, ML：± 1.00 mm,
DV：-2.5 mm.Postoperative recovery seven days, is grouped into later：Vehicle groups (10), CUS groups (30), wait for modeling in 5 weeks at
After work(, CUS group mouse are divided into Vehicle (10), NBQX+PF-4778574 (10), PF-4778574 (10).Brain
1 hour intraperitoneal administration PF-4778574 or Vehicle after ACSF or NBQX inject in portion, and spacious field experiment, new ring are carried out after 24 hours
Under border food rcstriction test, syrup preference experiment, forced swim test Behavior test and take brain tissue carry out molecule experiments
Detection, experiment detailed process are shown in Fig. 3.
In Behavior test, PF-4778574 (1 mg/kg) has significantly reversed the depressed mouse threading number that CUS is induced
(Fig. 7 A, P<0.01) with standing number (Fig. 7 B, P<0.01) reduction；And the depressed mouse for significantly having reversed CUS to induce
Forced swim test dead time (Fig. 7 C, P<0.05) incubation period (Fig. 7 E, P are tested with new environment food rcstriction< 0.01)
Increase；And significantly reverse behavior (Fig. 7 D, P of the depressed mouse anhedonia of CUS inductions< 0.01).But works as and give
When ampa receptor antagonist (NBQX) inhibits ampa receptor activation, then threading number (figure when giving PF-4778574 (1 mg/kg)
7A, P<0.01) with standing number (Fig. 7 B, P<0.01) conspicuousness reduces, and forced swim test dead time conspicuousness increases
Add (Fig. 7 C, P<0.05), and significantly reduce mouse syrup preference experiment in syrup drink percentage (Fig. 7 D, P<
0.01) incubation period (Fig. 7 E, P of the mouse in food rcstriction experiment, are increased<0.01) it, with CUS group mouse indifferences, says
Bright ampa receptor antagonist NBQX completely inhibits the antidepression behavior of PF-4778574.
It is found through experiments that do not occur substantially changeing work with the quick antidepressant effect of the drug prepared by PF-4778574
Kinetic force, and the quick antidepressant effect of single drug processing can continue week age.
Highly preferred embodiment of the present invention has been elucidated with, and the various change or remodeling made by those skilled in the art all will not
It departs from the scope of the present invention.
Claims (5)
1. a kind of application of ampa receptor agonist, it is characterized in that：The ampa receptor agonist is PF-4778574, knot
Structure formula is：
；
Molecular formula is：C19H22N2O3S2;Compound molecular weight is 390.52;Chemical name：N-[(3R,4S)-3-[4-(5-
Cyano-2-thienyl)phenyl]tetrahydro-2H-pyran-4-yl]-2-propanesulfonamide N-{(3R,
4S)-3-[4-(5-Cyano-2-thienyl)phenyl]tetrahydro-2H-pyran-4-yl}propane-2-
sulfonamide;The PF-4778574 is applied in quick antidepressant.
2. a kind of application of ampa receptor agonist according to claim 1, it is characterized in that：The quick antidepressants
In object, the dosage of PF-4778574 is 1mg/kg or 2mg/kg.
3. a kind of application of ampa receptor agonist according to claim 2, it is characterized in that：The quick antidepressants
Include PF-4778574 compounds or its drug acceptable salt in object.
4. a kind of application of ampa receptor agonist according to claim 3, it is characterized in that：The quick antidepressants
The administering mode of object is ejection preparation, oral preparation or external preparation.
5. a kind of application of ampa receptor agonist according to claim 4, it is characterized in that：The quick antidepressants
The dosage form of object includes tablet, capsule, powder, pill, granule, injection or emulsion.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110172297A1 (en) * | 2008-10-02 | 2011-07-14 | Pfizer Inc | Oxopiperdinyl And Pyranyl Sulfonamides and Pharmaceutical Compositions Thereof |
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2018
- 2018-07-17 CN CN201810781665.9A patent/CN108785304A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110172297A1 (en) * | 2008-10-02 | 2011-07-14 | Pfizer Inc | Oxopiperdinyl And Pyranyl Sulfonamides and Pharmaceutical Compositions Thereof |
Non-Patent Citations (2)
| Title |
|---|
| SEVERINE FARLEY等: "Antidepressant-like effects of an AMPA receptor potentiator under a chronic mild stress paradigm", 《INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY》 * |
| XIA LI等: "Antidepressant-like actions of an AMPA receptor potentiator(LY392098)", 《NEUROPHARMACOLOGY》 * |
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Application publication date: 20181113 |