Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic
Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue. Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus in...
Saved in:
| Published in | Frontiers in pharmacology Vol. 13; p. 830791 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Media S.A
03.02.2022
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Background:
The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.
Methods:
The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The
in vitro
metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition.
Results:
HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABA
A
) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABA
A
receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system.
Conclusions:
HSK3486 is a positive allosteric regulator and direct agonist of GABA
A
receptor. It has a promising sedative/hypnotic effect and good
in vivo
pharmacokinetic properties, which justify further studies towards its clinical application. |
|---|---|
| AbstractList | The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.
The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The
metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition.
HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABA
) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABA
receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system.
HSK3486 is a positive allosteric regulator and direct agonist of GABA
receptor. It has a promising sedative/hypnotic effect and good
pharmacokinetic properties, which justify further studies towards its clinical application. Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue. Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition. Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABA A ) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABA A receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system. Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABA A receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application. Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue. Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition. Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABAA) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABAA receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system. Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABAA receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application.Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue. Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition. Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABAA) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABAA receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system. Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABAA receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application. Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition.Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABAA) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABAA receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system.Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABAA receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application. |
| Author | Xiao, Jie Huang, Chaoli Chen, Yashu Liao, Juan Xiang, Guilin Li, Meiting Li, Peng Yang, Mengchang Yu, Yan Gan, Jiaqi Ding, Xizhi Jiang, Rong |
| AuthorAffiliation | 4 Haisco Pharmaceutical Group Co. Ltd. , Chengdu , China 1 Department of Stomatology , Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu , China 2 Department of Anesthesiology , Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu , China 3 East Hospital , Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu , China |
| AuthorAffiliation_xml | – name: 2 Department of Anesthesiology , Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu , China – name: 3 East Hospital , Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu , China – name: 1 Department of Stomatology , Sichuan Provincial People’s Hospital , University of Electronic Science and Technology of China , Chengdu , China – name: 4 Haisco Pharmaceutical Group Co. Ltd. , Chengdu , China |
| Author_xml | – sequence: 1 givenname: Juan surname: Liao fullname: Liao, Juan – sequence: 2 givenname: Meiting surname: Li fullname: Li, Meiting – sequence: 3 givenname: Chaoli surname: Huang fullname: Huang, Chaoli – sequence: 4 givenname: Yan surname: Yu fullname: Yu, Yan – sequence: 5 givenname: Yashu surname: Chen fullname: Chen, Yashu – sequence: 6 givenname: Jiaqi surname: Gan fullname: Gan, Jiaqi – sequence: 7 givenname: Jie surname: Xiao fullname: Xiao, Jie – sequence: 8 givenname: Guilin surname: Xiang fullname: Xiang, Guilin – sequence: 9 givenname: Xizhi surname: Ding fullname: Ding, Xizhi – sequence: 10 givenname: Rong surname: Jiang fullname: Jiang, Rong – sequence: 11 givenname: Peng surname: Li fullname: Li, Peng – sequence: 12 givenname: Mengchang surname: Yang fullname: Yang, Mengchang |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35185584$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kktP3DAUha2KqjzKD-imyrILMvUjduxNJQQUUFFbie6tG-eGMc3Y0zgZiX9fh2EQVKo3tq7v-Y4f55DshRiQkA-MLoTQ5nO3XsKw4JTzhRa0NuwNOWBKidJoxvderPfJcUr3NA9hjFDVO7IvJNNS6uqATD8zZQUutg8BVt6lAkJb7Iq_fcBxLsauuLr9JiqtTgoovscN9gU_UeW5T1OTRj9OI84yDLEvznHwGxj9BgvIvOISAw7QF6cB07icge_J2w76hMdP8xG5_Xrx6-yqvPlxeX12elO6SsmxBNEYSjmVrlNgFNJGQiM1GimB0QaACuxq4UTtuKtNxxtptDSVkU6zRhyR6y21jXBv14NfwfBgI3j7WIjDnYUhn6ZHWzkJgiIDIdrK1BzaWnTaOaGB61q5zPqyZa2nZoWtwzDmK72Cvt4Jfmnv4sZqLRmVOgM-PQGG-GfKD2FXPjnsewgYp2S5Ekxxkd1y68eXXs8mu1_LDfW2wQ0xpQE76_yYHzzO1r63jNo5IvYxInaOiN1GJCvZP8od_P-av50vv-4 |
| CitedBy_id | crossref_primary_10_1136_bmjopen_2022_071438 crossref_primary_10_2147_DDDT_S441950 crossref_primary_10_1186_s13741_024_00484_7 crossref_primary_10_1039_D3AY01168B crossref_primary_10_11648_j_cmr_20241306_14 crossref_primary_10_1136_bmjopen_2023_083068 crossref_primary_10_1007_s11096_022_01529_x crossref_primary_10_1007_s40261_025_01425_y crossref_primary_10_1080_07853890_2022_2129433 crossref_primary_10_1002_bdd_2368 crossref_primary_10_1007_s00228_024_03782_7 crossref_primary_10_3389_fmed_2022_1024762 crossref_primary_10_2147_DDDT_S478994 crossref_primary_10_12998_wjcc_v11_i3_487 crossref_primary_10_1111_cts_13605 crossref_primary_10_3389_fmed_2025_1539238 crossref_primary_10_23736_S0375_9393_24_18263_6 crossref_primary_10_36502_2024_ASJBCCR_6353 crossref_primary_10_1186_s12871_025_02986_3 crossref_primary_10_2147_DDDT_S496783 crossref_primary_10_1097_ALN_0000000000004886 crossref_primary_10_1186_s12871_024_02583_w crossref_primary_10_2147_DDDT_S414166 crossref_primary_10_3389_fphar_2022_1091579 crossref_primary_10_1111_bcp_15561 crossref_primary_10_1186_s12871_024_02479_9 crossref_primary_10_1186_s13613_024_01390_3 crossref_primary_10_2147_DDDT_S505772 crossref_primary_10_1111_bcp_15822 crossref_primary_10_1186_s12871_024_02609_3 crossref_primary_10_1371_journal_pone_0307995 crossref_primary_10_1097_CCM_0000000000005920 crossref_primary_10_1007_s10620_023_08213_8 crossref_primary_10_1186_s12871_024_02787_0 crossref_primary_10_1038_s41598_025_85968_2 crossref_primary_10_1177_03000605221132466 crossref_primary_10_3389_fphar_2025_1572112 crossref_primary_10_1155_2023_7443226 crossref_primary_10_1186_s12890_024_03415_w |
| Cites_doi | 10.1097/00000542-199301000-00015 10.1097/00000542-200411000-00017 10.1021/acs.jmedchem.7b00254 10.1213/ane.0b013e31818fc334 10.1097/00000542-199701000-00010 10.1016/0006-2952(73)90196-2 10.1016/j.vascn.2014.08.006 10.1016/0304-3835(83)90208-2 10.1016/j.cell.2018.08.031 10.3791/51079 10.1097/ALN.0b013e318289bcd3 10.1186/s12917-018-1608-8 10.2307/2348094 10.1016/0920-1211(90)90039-x 10.1093/bja/aen169 10.1213/ANE.0000000000001580 10.1002/(SICI)1097-0010(199802)76:2<270::AID-JSFA945>3.0.CO;2-9 10.1007/s004240000289 10.4103/0253-7613.194845 10.1016/0006-8993(87)90017-5 10.1111/anae.13578 10.1177/0885066610384195 10.1097/00000539-199507000-00025 10.1006/abio.2001.5395 10.1021/jm00186a013 10.1097/00000539-199603000-00007 |
| ContentType | Journal Article |
| Copyright | Copyright © 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang. Copyright © 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang. 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang |
| Copyright_xml | – notice: Copyright © 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang. – notice: Copyright © 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang. 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang |
| DBID | AAYXX CITATION NPM 7X8 5PM DOA |
| DOI | 10.3389/fphar.2022.830791 |
| DatabaseName | CrossRef PubMed MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed CrossRef MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| DocumentTitleAlternate | Liao et al |
| EISSN | 1663-9812 |
| ExternalDocumentID | oai_doaj_org_article_4c5a30e1a33d4972ad73f8cc38a2876c PMC8851058 35185584 10_3389_fphar_2022_830791 |
| Genre | Journal Article |
| GroupedDBID | 53G 5VS 9T4 AAFWJ AAKDD AAYXX ACGFO ACGFS ACXDI ADBBV ADRAZ AENEX AFPKN ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BCNDV CITATION DIK EMOBN GROUPED_DOAJ GX1 HYE KQ8 M48 M~E O5R O5S OK1 P2P PGMZT RNS RPM IAO IEA IHR IHW IPNFZ NPM RIG 7X8 5PM |
| ID | FETCH-LOGICAL-c465t-a3b900205cf6a96e0b5ab58e955a10baa03ef73c37c2c79f2b59859495c81b3 |
| IEDL.DBID | M48 |
| ISSN | 1663-9812 |
| IngestDate | Wed Aug 27 01:31:33 EDT 2025 Thu Aug 21 14:03:51 EDT 2025 Fri Jul 11 12:34:34 EDT 2025 Thu Jan 02 22:55:00 EST 2025 Tue Jul 01 03:27:51 EDT 2025 Thu Apr 24 23:10:49 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | GABA pharmacokinetics sedation pharmacodynamics anesthesia |
| Language | English |
| License | Copyright © 2022 Liao, Li, Huang, Yu, Chen, Gan, Xiao, Xiang, Ding, Jiang, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c465t-a3b900205cf6a96e0b5ab58e955a10baa03ef73c37c2c79f2b59859495c81b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Youssef Jounaidi, Massachusetts General Hospital and Harvard Medical School, United States These authors have contributed equally to this work Edited by: Apostolos Zarros, University of Glasgow, United Kingdom Gustav Akk, Washington University in St. Louis, United States This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology |
| OpenAccessLink | http://journals.scholarsportal.info/openUrl.xqy?doi=10.3389/fphar.2022.830791 |
| PMID | 35185584 |
| PQID | 2631623287 |
| PQPubID | 23479 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_4c5a30e1a33d4972ad73f8cc38a2876c pubmedcentral_primary_oai_pubmedcentral_nih_gov_8851058 proquest_miscellaneous_2631623287 pubmed_primary_35185584 crossref_citationtrail_10_3389_fphar_2022_830791 crossref_primary_10_3389_fphar_2022_830791 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2022-02-03 |
| PublicationDateYYYYMMDD | 2022-02-03 |
| PublicationDate_xml | – month: 02 year: 2022 text: 2022-02-03 day: 03 |
| PublicationDecade | 2020 |
| PublicationPlace | Switzerland |
| PublicationPlace_xml | – name: Switzerland |
| PublicationTitle | Frontiers in pharmacology |
| PublicationTitleAlternate | Front Pharmacol |
| PublicationYear | 2022 |
| Publisher | Frontiers Media S.A |
| Publisher_xml | – name: Frontiers Media S.A |
| References | Qin (B23) 1983; 21 Doenicke (B9) 1996; 82 Chandramani Saxena (B4) 2000; 440 Robinson (B25) 1997; 86 Anderson (B1) 1974; 33 Desousa (B16) 2016; 48 Cheng (B5) 1973; 22 Van Rijn (B29) 1990; 5 Qin (B22) 2017; 60 Rochette (B26) 2008; 101 Qiu (B24) 2016; 71 Gadagkar (B10) 2015; 71 Sánchez-Moreno (B27) 1998; 76 (B13) 2011 Squires (B28) 1987; 414 Diedrich (B8) 2011; 26 Nithipatikom (B20) 2001; 298 Andrea (B2) 2018; 14 Li (B17) 2013; 118 Wouters (B30) 1995; 81 Pagel (B21) 1993; 78 Besnier (B3) 2017; 124 Grasshoff (B11) 2004; 101 Maria (B18) 2020; 46 James (B14) 1980; 23 D'Enes (B7) 1992; 41 Walsh (B15) 2018; 175 Cravero (B6) 2009; 108 Mccarren (B19) 2013 Han (B12) 2013; 38 |
| References_xml | – volume: 78 start-page: 100 year: 1993 ident: B21 article-title: Negative Inotropic Effects of Propofol as Evaluated by the Regional Preload Recruitable Stroke Work Relationship in Chronically Instrumented Dogs publication-title: Anesthesiology doi: 10.1097/00000542-199301000-00015 – volume: 101 start-page: 1167 year: 2004 ident: B11 article-title: Propofol and Sevoflurane Depress Spinal Neurons In Vitro via Different Molecular Targets publication-title: Anesthesiology doi: 10.1097/00000542-200411000-00017 – volume: 60 start-page: 3606 year: 2017 ident: B22 article-title: Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics publication-title: J. Med. Chem. doi: 10.1021/acs.jmedchem.7b00254 – volume: 108 start-page: 795 year: 2009 ident: B6 article-title: The Incidence and Nature of Adverse Events during Pediatric Sedation/Anesthesia with Propofol for Procedures outside the Operating Room: A Report from the Pediatric Sedation Research Consortium publication-title: Anesth. Analgesia doi: 10.1213/ane.0b013e31818fc334 – volume: 86 start-page: 64 year: 1997 ident: B25 article-title: Mechanisms Whereby Propofol Mediates Peripheral Vasodilation in Humans. Sympathoinhibition or Direct Vascular Relaxation? publication-title: Anesthesiology doi: 10.1097/00000542-199701000-00010 – volume: 22 start-page: 3099 year: 1973 ident: B5 article-title: Relationship between the Inhibition Constant (K1) and the Concentration of Inhibitor Which Causes 50% Inhibition (EC) of Enzyme Reaction publication-title: Biochem. Pharmacol. doi: 10.1016/0006-2952(73)90196-2 – volume: 71 start-page: 68 year: 2015 ident: B10 article-title: Computational Tools for Fitting the Hill Equation to Dose-Response Curves publication-title: J. Pharmacol. Toxicol. Methods doi: 10.1016/j.vascn.2014.08.006 – volume: 21 start-page: 201 year: 1983 ident: B23 article-title: Inhibition of Retinoid Toxicity by Rat Liver S9 Fraction in Cultured Mammalian Cells publication-title: Cancer Lett. doi: 10.1016/0304-3835(83)90208-2 – volume: 33 start-page: 1036 year: 1974 ident: B1 article-title: Institute of Laboratory Animal Resources publication-title: Fed. Proc. – volume: 175 start-page: 10 year: 2018 ident: B15 article-title: Propofol: Milk of Amnesia publication-title: Cell doi: 10.1016/j.cell.2018.08.031 – start-page: e51079 year: 2013 ident: B19 article-title: Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention publication-title: J. Vis. Exp. doi: 10.3791/51079 – volume: 118 start-page: 1417 year: 2013 ident: B17 article-title: The Benzodiazepine Diazepam Potentiates Responses of α1β2γ2L γ-aminobutyric Acid Type A Receptors Activated by Either γ-aminobutyric Acid or Allosteric Agonists publication-title: Anesthesiology doi: 10.1097/ALN.0b013e318289bcd3 – volume: 46 start-page: 365 year: 2020 ident: B18 article-title: Determination of the Acyl Glucuronide Metabolite of Mycophenolic Acid in Human Plasma by HPLC and Emit publication-title: Clin. Chem. – volume: 14 start-page: 282 year: 2018 ident: B2 article-title: Haemodynamic Changes during Propofol Induction in Dogs: New Findings and Approach of Monitoring publication-title: BMC Vet. Res. doi: 10.1186/s12917-018-1608-8 – volume: 41 start-page: 601 year: 1992 ident: B7 article-title: New Developments in the Theory and Applications publication-title: Appl. Stat. doi: 10.2307/2348094 – volume: 5 start-page: 199 year: 1990 ident: B29 article-title: Folates: Epileptogenic Effects and Enhancing Effects on [3H]TBOB Binding to the GABAA-Receptor Complex publication-title: Epilepsy Res. doi: 10.1016/0920-1211(90)90039-x – volume: 101 start-page: 390 year: 2008 ident: B26 article-title: Avoiding Propofol Injection Pain in Children: a Prospective, Randomized, Double-Blinded, Placebo-Controlled Study publication-title: Br. J. Anaesth. doi: 10.1093/bja/aen169 – volume: 124 start-page: 1181 year: 2017 ident: B3 article-title: The Hypothalamic-Pituitary-Adrenal Axis and Anesthetics: A Review publication-title: Anesth. Analg doi: 10.1213/ANE.0000000000001580 – volume: 76 start-page: 270 year: 1998 ident: B27 article-title: A Procedure to Measure the Antiradical Efficiency of Polyphenols publication-title: J. Sci. Food Agric. doi: 10.1002/(SICI)1097-0010(199802)76:2<270::AID-JSFA945>3.0.CO;2-9 – volume: 440 start-page: 380 year: 2000 ident: B4 article-title: Inhibition of GABAA Receptor (GABAR) Currents by Arachidonic Acid in HEK 293 Cells Stably Transfected with α1β2γ2 GABAR Subunits publication-title: Pflugers Arch. - Eur. J. Physiol. doi: 10.1007/s004240000289 – start-page: 963 volume-title: Guide for the Care and Use of Laboratory Animals year: 2011 ident: B13 article-title: National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals – volume: 48 start-page: 617 year: 2016 ident: B16 article-title: Pain on Propofol Injection: Causes and Remedies publication-title: Indian J. Pharmacol. doi: 10.4103/0253-7613.194845 – volume: 414 start-page: 357 year: 1987 ident: B28 article-title: GABAA Receptor Blockers Reverse the Inhibitory Effect of GABA on Brain-specific [35S]TBPS Binding publication-title: Brain Res. doi: 10.1016/0006-8993(87)90017-5 – volume: 71 start-page: 1222 year: 2016 ident: B24 article-title: Effects of Intra-operative Maintenance of General Anaesthesia with Propofol on Postoperative Pain Outcomes - a Systematic Review and Meta-Analysis publication-title: Anaesthesia doi: 10.1111/anae.13578 – volume: 26 start-page: 59 year: 2011 ident: B8 article-title: Analytic Reviews: Propofol Infusion Syndrome in the ICU publication-title: J. Intensive Care Med. doi: 10.1177/0885066610384195 – volume: 38 start-page: 432 year: 2013 ident: B12 article-title: Determination of Plasma Protein Binding Rate of Arctiin and Arctigenin with Ultrafiltration publication-title: Zhongguo Zhong Yao Za Zhi – volume: 81 start-page: 125 year: 1995 ident: B30 article-title: Hemodynamic Changes during Induction of Anesthesia with Eltanolone and Propofol in Dogs publication-title: Anesth. Analg doi: 10.1097/00000539-199507000-00025 – volume: 298 start-page: 327 year: 2001 ident: B20 article-title: Liquid Chromatographic-Electrospray Ionization-Mass Spectrometric Analysis of Cytochrome P450 Metabolites of Arachidonic Acid publication-title: Anal. Biochem. doi: 10.1006/abio.2001.5395 – volume: 23 start-page: 1350 year: 1980 ident: B14 article-title: Synthesis, Biological Evaluation, and Preliminary Structure-Activity Considerations of a Series of Alkylphenols as Intravenous Anesthetic Agents publication-title: J. Med. Chem. doi: 10.1021/jm00186a013 – volume: 82 start-page: 472 year: 1996 ident: B9 article-title: Reducing Pain during Propofol Injection: The Role of the Solvent publication-title: Anesth. Analg doi: 10.1097/00000539-199603000-00007 |
| SSID | ssj0000399364 |
| Score | 2.525117 |
| Snippet | Background:
The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.
Methods:
The... The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue. The mechanism of action of... Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue. Methods: The... Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.Methods: The... |
| SourceID | doaj pubmedcentral proquest pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 830791 |
| SubjectTerms | anesthesia GABA pharmacodynamics pharmacokinetics Pharmacology sedation |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEBYlp15K33XbFBVKDmXd2BrrdUybhqWlIZAUchOSLJGQxQ7d3UD-fUaWd7NbSnvp0fZIFpqR5hs0-oaQD6DBK9myMrLAygZ9XOl40KVzGnjlotUiXU7-cSymP5tv5_x8o9RXygnL9MB54vYbzy1UobYAbaMls62EqLwHZRHsC592X_R5G8HUsAcnvyuafIyJUZjej9cXNvF_MvZJoV3ressRDXz9fwKZv-dKbjifo8fk0Yga6UEe7RPyIHRPyd5Jpp2-ndCz-1tU8wndoyf3hNS3z8hy9djm8vNzart2LXOFODO1o32k09Pv0CgxoZYe9zdhRtlElIeXc9xdckpBaha6fkYP0XJvBtJwarE_OtJX0wPcOhFTYofPyenR17Mv03Ist1B61NGitOB0Qo_cR4EqCpXj1nEVNOe2rpy1FYQowYP0zEsdmeNacY0RlkfsCy_ITtd34RWh6OFEK7xodZ3Y6qSuNKujjSzKWNe6LUi1mnnjRybyVBBjZjAiScoyg7JMUpbJyirIx3WT60zD8Tfhz0mda8HEoD28QLsyo12Zf9lVQd6vjMHgikvHKLYL_XJumIAaQSNKFeRlNo71r4Aj_kFMVxC5ZTZbY9n-0l1eDKzeSiWsq17_j8G_IQ_TfAzZ5fCW7Cx-LcMugqeFezeskzvoDxh_ priority: 102 providerName: Directory of Open Access Journals |
| Title | Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/35185584 https://www.proquest.com/docview/2631623287 https://pubmed.ncbi.nlm.nih.gov/PMC8851058 https://doaj.org/article/4c5a30e1a33d4972ad73f8cc38a2876c |
| Volume | 13 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEBYhvfRS-q77CCqUHMo6tSXrdSglbRqWloRAEsjNSLKUhC52ut4N3X_fGdu76Zalpx5tz9hCM9J8Y0nfEPKOG-61qlgaWWBpATEudSKY1DnDReaiNRIPJx8dy_F58e1CXGyRZXmroQPbjakd1pM6n072fv1cfIIB_xEzToi3H-LNlUVqT8b2NLgsnmW_B4FJYUGDowHtdxMzBmNZ9GubmzXXolNH4r8Jef69gfKPiHT4kDwYoCTd723_iGyF-jHZPem5qBcjenZ3tKod0V16csdSvXhC5svLqq9J31JbVyuZHwA-UY82kY5Pv_NCyxG19Li5DRPKRjI9uG5hyun3GaBaqJsJPQB3vu2YxKmF99GB05ruw3wKQBNe-JScHn49-zJOhxoMqQfDzVLLnUFIKXyUYLeQOWGd0MEIYfPMWZvxEBX3XHnmlYnMCaOFgbTLAyDmz8h23dThBaEQ9mQlvaxMjhR2ymSG5dFGFlXMc1MlJFv2fOkHenKskjEpIU1BY5WdsUo0VtkbKyHvVyo3PTfHv4Q_ozlXgkir3d1oppflMErLwgvLs5BbzqvCKGYrxaP2nmsLmaX0CXm7dIYShiGurdg6NPO2ZJLngCRBKiHPe-dYfYoLAEUA9BKi1txmrS3rT-rrq47qW2sEwPrl_2j8K3If-6Pbcs5fk-3ZdB7eAKKauZ3uT8RON1p-AxI7IcU |
| linkProvider | Scholars Portal |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pharmacodynamics+and+Pharmacokinetics+of+HSK3486%2C+a+Novel+2%2C6-Disubstituted+Phenol+Derivative+as+a+General+Anesthetic&rft.jtitle=Frontiers+in+pharmacology&rft.au=Juan+Liao&rft.au=Meiting+Li&rft.au=Chaoli+Huang&rft.au=Yan+Yu&rft.date=2022-02-03&rft.pub=Frontiers+Media+S.A&rft.eissn=1663-9812&rft.volume=13&rft_id=info:doi/10.3389%2Ffphar.2022.830791&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_4c5a30e1a33d4972ad73f8cc38a2876c |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1663-9812&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1663-9812&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1663-9812&client=summon |