インバースアゴニスト、逆作動薬、逆刺激薬、逆作用薬
WordNet
- opposite in nature or effect or relation to another quantity ; "a term is in inverse proportion to another term if it increases (or decreases) as the other decreases (or increases)"
- something inverted in sequence or character or effect; "when the direct approach failed he tried the inverse" (同)opposite
- reversed (turned backward) in order or nature or effect (同)reverse
- (biochemistry) a drug that can combine with a receptor on a cell to produce a physiological reaction
- a muscle that contracts while another relaxes; "when bending the elbow the biceps are the agonist"
- someone involved in a contest or battle (as in an agon)
PrepTutorEJDIC
- (順序・位置・方向などが)逆の,反対の / (…の)逆,反対[のもの]《+『of』+『名』》 / 逆数
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2016/08/22 03:15:12」(JST)
[Wiki en表示]
Dose response curves of a full agonist, partial agonist, neutral antagonist, and inverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.[1]
A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level activity in the absence of any ligand. An agonist increases the activity of a receptor above its basal level, whereas an inverse agonist decreases the activity below the basal level.
The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy, and an inverse agonist has < 0% (i.e., negative) efficacy.
Contents
- 1 Examples
- 2 See also
- 3 References
- 4 Further reading
- 5 External links
Examples
An example of a receptor that possesses basal activity and for which inverse agonists have been identified is the GABAA receptor. Agonists for the GABAA receptor (such as benzodiazepines) create a sedative effect, whereas inverse agonists have anxiogenic effects (for example, Ro15-4513) or even convulsive effects (certain beta-carbolines).[2][3]
Two known endogenous inverse agonists are the Agouti-related peptide (AgRP) and its associated peptide Agouti signalling peptide (ASIP). Both appear naturally in humans, and each binds melanocortin receptors 4 and 1 (Mc4R and Mc1R), respectively, with nanomolar affinities.[4]
The opioid antagonists naloxone and naltrexone are also partial inverse agonists at mu opioid receptors.
See also
- Agonist
- Receptor antagonist
References
- ^ Kenakin T (April 2004). "Principles: receptor theory in pharmacology". Trends in Pharmacological Sciences. 25 (4): 186–92. doi:10.1016/j.tips.2004.02.012. PMID 15063082.
- ^ Mehta AK, Ticku MK (August 1988). "Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels". The Journal of Pharmacology and Experimental Therapeutics. 246 (2): 558–64. PMID 2457076.
- ^ Sieghart W (January 1994). "Pharmacology of benzodiazepine receptors: an update". Journal of Psychiatry & Neuroscience. 19 (1): 24–9. PMC 1188559. PMID 8148363.
- ^ Ollmann MM, Lamoreux ML, Wilson BD, Barsh GS (February 1998). "Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo". Genes & Development. 12 (3): 316–30. doi:10.1101/gad.12.3.316. PMC 316484. PMID 9450927.
Further reading
- Khilnani G, Khilnani AK (September 2011). "Inverse agonism and its therapeutic significance". Indian Journal of Pharmacology. 43 (5): 492–501. doi:10.4103/0253-7613.84947. PMC 3195115. PMID 22021988.
External links
- Jeffries WB (1999-02-17). "Inverse Agonists for Medical Students". Office of Medical Education - Courses - IDC 105 Principles of Pharmacology. Creighton University School of Medicine - Department of Pharmacology. Retrieved 2008-08-12.
- Inverse Agonists: An Illustrated Tutorial Panesar K, Guzman F. Pharmacology Corner. 2012
Concepts in pharmacology
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Pharmacokinetics |
- (L)ADME: (Liberation)
- Absorption
- Distribution
- Metabolism
- Excretion (Clearance)
- Loading dose
- Volume of distribution (Initial)
- Rate of infusion
- Compartment
- Bioequivalence
- Bioavailability
- Onset of action
- Biological half-life
- Plasma protein binding
- Therapeutic index (Median lethal dose, Effective dose)
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Pharmacodynamics |
- Toxicity (Neurotoxicology)
- Dose–response relationship (Efficacy, Potency)
- Antimicrobial pharmacodynamics: Minimum inhibitory concentration (Bacteriostatic)
- Minimum bactericidal concentration (Bactericide)
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Agonism and
antagonism |
- Agonist: Inverse agonist
- Irreversible agonist
- Partial agonist
- Superagonist
- Physiological agonist
- Antagonist: Competitive antagonist
- Irreversible antagonist
- Physiological antagonist
- Other: Binding
- Affinity
- Binding selectivity
- Functional selectivity
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Other |
- Drug tolerance: Tachyphylaxis
- Drug resistance: Antibiotic resistance
- Multiple drug resistance
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Drug discovery
strategies |
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Related
fields/subfields |
- Pharmacogenetics
- Pharmacogenomics
- Neuropsychopharmacology (Neuropharmacology, Psychopharmacology)
|
UpToDate Contents
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English Journal
- Detection, characterization and biological activities of [bisphospho-thr(3,9)]ODN, an endogenous molecular form of ODN released by astrocytes.
- Gach K1, Belkacemi O2, Lefranc B3, Perlikowski P4, Masson J5, Walet-Balieu ML5, Do-Rego JC6, Galas L3, Schapman D3, Lamtahri R2, Tonon MC2, Vaudry D7, Chuquet J2, Leprince J8.
- Neuroscience.Neuroscience.2015 Apr 2;290:472-84. doi: 10.1016/j.neuroscience.2015.01.045. Epub 2015 Jan 30.
- Astrocytes synthesize and release endozepines, a family of regulatory neuropeptides, including diazepam-binding inhibitor (DBI) and its processing fragments such as the octadecaneuropeptide (ODN). At the molecular level, ODN interacts with two types of receptors, i.e. it acts as an inverse agonist o
- PMID 25639232
- Novel 4-substituted-N,N-dimethyltetrahydronaphthalen-2-amines: synthesis, affinity, and in silico docking studies at serotonin 5-HT2-type and histamine H1 G protein-coupled receptors.
- Sakhuja R1, Kondabolu K1, Córdova-Sintjago T2, Travers S1, Vincek AS1, Kim MS1, Abboud KA1, Fang L1, Sun Z1, Canal CE2, Booth RG3.
- Bioorganic & medicinal chemistry.Bioorg Med Chem.2015 Apr 1;23(7):1588-600. doi: 10.1016/j.bmc.2015.01.060. Epub 2015 Feb 7.
- Syntheses were undertaken of derivatives of (2S,4R)-(-)-trans-4-phenyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (4-phenyl-2-dimethylaminotetralin, PAT), a stereospecific agonist at the serotonin 5-HT2C G protein-coupled receptor (GPCR), with inverse agonist activity at 5-HT2A and 5-HT2B GPC
- PMID 25703249
- Agonist binding by the β2-adrenergic receptor: an effect of receptor conformation on ligand association-dissociation characteristics.
- Plazinska A1, Plazinski W, Jozwiak K.
- European biophysics journal : EBJ.Eur Biophys J.2015 Apr;44(3):149-63. doi: 10.1007/s00249-015-1010-4. Epub 2015 Mar 1.
- The β2-adrenergic receptor (β2-AR), a G protein-coupled receptor (GPCR), is a physiologically important transmembrane protein that is a target for drugs used for treatment of asthma and cardiovascular diseases. Study of the first steps of ligand recognition and the molecular basis of ligand bindin
- PMID 25726162
Japanese Journal
- アレルギー性鼻炎におけるヒスタミンH₁受容体遺伝子発現亢進の分子機構とその制御
- アレルギー性鼻炎におけるヒスタミンH₁受容体の役割 (特集 アレルギー性鼻炎の発症メカニズム)
- Single-molecule observation of the ligand-induced population shift of rhodopsin, a g-protein-coupled receptor.
- Maeda Ryo,Hiroshima Michio,Yamashita Takahiro,Wada Akimori,Nishimura Shoko,Sako Yasushi,Shichida Yoshinori,Imamoto Yasushi
- Biophysical journal 106(4), 915-924, 2014-02-18
- … Rhodopsin is a G-protein-coupled receptor, in which retinal chromophore acts as inverse-agonist or agonist depending on its configuration and protonation state. …
- NAID 120005399103
Related Links
- inverse agonist 受容体に結合し恒常的活性を減弱させる物質。一般に、受容体は不活性型で存在し、アゴニストと結合することにより活性型に変化し機能発現する。しかしながら、ある種の受容体(たとえばGABA A 受容体)はアゴニストが ...
- インバースアゴニスト:逆作動薬 インバースアゴニストとは インバースアゴニストは英語で「inverse agonist」と書く。そして、「inverse」とは「逆の」という意味がある。つまり、アゴニストは受容体の刺激薬であるが、それと逆の作用 ...
Related Pictures
★リンクテーブル★
[★]
- 英
- inverse agonist
- 同
- 逆作動薬
- 関
- アゴニスト、部分アゴニスト
GOO. 23,25-26,37
- レセプターには少なくと2つの構造的な状態、活性化した構造と不活性化した構造がある (GOO.25)
- 薬剤がいずれの構造に強く結合するかで、完全アゴニスト、部分アゴニスト、不活性物質、インバースアゴニストに分けられる (GOO.25)
- 作用はアゴニストの反対の作用を示す
- ここが非競合的なアンタゴニストと異なる
[★]
- 英
- inverse agonist
- 関
- インバースアゴニスト、逆作用薬、逆刺激薬
[★]
- 英
- inverse agonist
- 関
- インバースアゴニスト、逆作動薬、逆刺激薬
[★]
- 英
- inverse agonist
- 関
- インバースアゴニスト、逆作動薬、逆作用薬
[★]
- 関
- adversely、backward、converse、conversely、inversely、inversion、invert、opposite、oppositely、retro、reversal、reverse