histamine H1 antagonist

• ヒスタミンH1受容体遮断薬、ヒスタミンH1拮抗薬、ヒスタミンH1遮断薬

関

antihistamine、H1 blocker、histamine H1 receptor antagonist

WordNet

1. a medicine used to treat allergies and hypersensitive reactions and colds; works by counteracting the effects of histamine on a receptor site
2. a drug that neutralizes or counteracts the effects of another drug
3. a muscle that relaxes while another contracts; "when bending the elbow the triceps are the antagonist"
4. the 8th letter of the Roman alphabet (同)h
5. amine formed from histidine that stimulates gastric secretions and dilates blood vessels; released by the human immune system during allergic reactions

PrepTutorEJDIC

1. 抗ヒスタミン剤(各種のアレルギー症・風邪の治療に用いる)
2. 対立する人,敵対者,競争相手(opponent)
3. hydrogenの化学記号
4. 鉛筆の硬度 / 《俗》heroin
5. ヒスタミン(子宮収縮・血圧降下の薬)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/01/24 02:35:56」(JST)

wiki en

[Wiki en表示]

H₁ antagonists, also called H₁ blockers, are a class of medications that block the action of histamine at the H₁ receptor, helping relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

In common use, the term "antihistamine" refers only to H₁ antagonists, also known as H₁-receptor antagonists and H₁-antihistamines. It has been discovered that some H₁-antihistamines function as inverse agonists, as opposed to receptor antagonists, at the histamine H₁-receptor.

Pharmacology

In type I hypersensitivity allergic reactions, an allergen (a type of antigen) interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, the histamine can react with local or widespread tissues through histamine receptors.

Histamine, acting on H₁-receptors, produces pruritus, vasodilation, hypotension, flushing, headache, tachycardia, bronchoconstriction, increase in vascular permeability and potentiation of pain.

While H₁-antihistamines help against these effects, they work only if taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects may be of life-threatening severity. Additional administration of epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivities.

Clinical use of H₁-antihistamines

Indications

H₁-antihistamines are clinically used in the treatment of histamine-mediated allergic conditions. These indications may include:

• Allergic rhinitis
• Allergic conjunctivitis
• Allergic dermatological conditions (contact dermatitis)
• Rhinorrhea (Runny nose)
• Urticaria
• Angioedema
• Diarrhea
• Pruritus (atopic dermatitis, insect bites)
• Anaphylactic or anaphylactoid reactions—adjunct only
• Nausea and vomiting
• Sedation (first-generation H₁-antihistamines)

H₁-antihistamines can be administered topically (through the skin, nose, or eyes) or systemically, based on the nature of the allergic condition.

The authors of the American College of Chest Physicians Updates on Cough Guidelines (2006) recommend that, for cough associated with the common cold, first-generation antihistamine-decongestants are more effective than newer, non-sedating antihistamines. First-generation antihistamines include diphenhydramine (Benadryl), carbinoxamine (Clistin), clemastine (Tavist), chlorpheniramine (Chlor-Trimeton), and brompheniramine (Dimetane). However, a 1955 study of "antihistaminic drugs for colds," carried out by the U.S. Army Medical Corps, reported that "there was no significant difference in the proportion of cures reported by patients receiving oral antihistaminic drugs and those receiving oral placebos. Furthermore, essentially the same proportion of patients reported no benefit from either type of treatment."

Adverse drug reactions

Adverse drug reactions are most commonly associated with the first-generation H₁-antihistamines. This is due to their relative lack of selectivity for the H₁-receptor and their ability to cross the blood-brain barrier.

The most common adverse effect is sedation; this "side-effect" is utilized in many OTC sleeping-aid preparations. Other common adverse effects in first-generation H₁-antihistamines include dizziness, tinnitus, blurred vision, euphoria, uncoordination, anxiety, increased appetite leading to weight gain, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, and psychosis.

The newer, second-generation H₁-antihistamines are far more selective for peripheral histamine H₁-receptors and have a better tolerability profile compared to the first-generation agents. The most common adverse effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth.

First-generation (non-selective, classical)

These are the oldest H₁-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor (anticholinergic) antagonists as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor selectivity is the basis of the poor tolerability profile of some of these agents, especially when compared with the second-generation H₁-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes.

Classes

The first H₁-antihistamine discovered was piperoxan, by Ernest Fourneau and Daniel Bovet (1933) in their efforts to develop a guinea pig animal model for anaphylaxis at the Pasteur Institute in Paris. Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution. Following their discovery, the first-generation H₁-antihistamines were developed in the following decades. They can be classified on the basis of chemical structure, and agents within these groups have similar properties.

Class	Description	Examples
Ethylenediamines	Ethylenediamines were the first group of clinically effective H1-antihistamines developed.	Mepyramine (pyrilamine) Chloropyramine Antazoline Tripelennamine
Ethanolamines	Diphenhydramine was the prototypical agent in this group. Significant anticholinergic adverse effects, as well as sedation, are observed in this group but the incidence of gastrointestinal adverse effects is relatively low.	Diphenhydramine Carbinoxamine Doxylamine Orphenadrine Bromazine Clemastine Dimenhydrinate
Alkylamines	The isomerism is a significant factor in the activity of the agents in this group. E-triprolidine, for example, is 1000-fold more potent than Z-triprolidine. This difference relates to the positioning and fit of the molecules in the histamine H1-receptor binding site. Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical central nervous system (CNS) stimulation.	Pheniramine Chlorphenamine (chlorpheniramine) Dexchlorpheniramine Dexbrompheniramine Brompheniramine Triprolidine Dimetindene
Piperazines	These compounds are structurally related to the ethylenediamines and the ethanolamines, and produce significant anticholinergic adverse effects. Compounds from this group are often used for motion sickness, vertigo, nausea, and vomiting. The second-generation H1-antihistamine cetirizine also belongs to this chemical group.	Cyclizine Chlorcyclizine Hydroxyzine Meclizine
Tricyclics and Tetracyclics	These compounds differ from the phenothiazine antipsychotics in the ring-substitution and chain characteristics. They are also structurally related to the tricyclic antidepressants (and tetracyclics), explaining the H1-antihistaminergic adverse effects of those three drug classes and also the poor tolerability profile of tricyclic H1-antihistamines. The second-generation H1-antihistamine loratadine was derived from compounds in this group.	Promethazine Alimemazine (trimeprazine) Cyproheptadine Azatadine

Common structural features

• Two aromatic rings, connected to a central carbon, nitrogen or CO
• Spacer between the central X and the amine, usually 2–3 carbons in length, linear, ring, branched, saturated or unsaturated
• Amine is substituted with small alkyl groups, e.g., CH₃

X = N, R1 = R2 = small alkyl groups
X = C
X = CO

• Chirality at X can increase both the potency and selectivity for H1-receptors
• For maximum potency, the two aromatic rings should be orientated in different planes
  • for example, tricyclic ring system is slightly puckered and the two aromatic rings lie in different geometrical planes, giving the drug a very high potency.

Second-generation and third-generation (selective, non-sedating)

Second-generation

Second-generation H₁-antihistamines are newer drugs that are much more selective for peripheral H₁ receptors as opposed to the central nervous system H₁ receptors and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief of allergic conditions. The reason for their peripheral selectivity is that most of these compounds are zwitterionic at physiological pH (around pH 7.4). As such, they are very polar, meaning that they do not cross the blood–brain barrier and act mainly outside the central nervous system.

Examples -

Systemic:

• Astemizole
• Ketotifen
• Cetirizine
• Loratadine
• Rupatadine
• Mizolastine
• Acrivastine
• Ebastine
• Bilastine
• Bepotastine
• Terfenadine
• Quifenadine

Topical:

• Azelastine
• Levocabastine
• Olopatadine

Third-generation

Third-generation H₁-antihistamines are second-generation antihistamines informally labeled third-generation because the active enantiomer (levocetirizine) or metabolite (desloratadine & fexofenadine) derivatives of second-generation drugs are intended to have increased efficacy with fewer adverse drug reactions. Fexofenadine is associated with a decreased risk of cardiac arrhythmia compared to terfenadine. However, there is little evidence for any advantage of levocetirizine or desloratadine, compared to cetirizine or loratadine, respectively.

There is some controversy associated with the use of the term third-generation antihistamines.

Examples -

Systemic:

• Levocetirizine
• Desloratadine
• Fexofenadine

References

External links

• Antihistaminics, H1 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. アレルギーのin vitro検査の概要 overview of in vitro allergy tests
• 2. スコンブロイド（ヒスタミン）中毒 scombroid histamine poisoning
• 3. アナフィラキシーの臨床診断を裏付ける臨床検査 laboratory tests to support the clinical diagnosis of anaphylaxis
• 4. 肝性脳症：病因 hepatic encephalopathy pathogenesis
• 5. 肥満細胞由来のメディエーター mast cell derived mediators

English Journal

• Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors.

• Sadek B1, Khanian SS1, Ashoor A1, Prytkova T2, Ghattas MA3, Atatreh N3, Nurulain SM1, Yang KH2, Howarth FC4, Oz M5.
• European journal of pharmacology.Eur J Pharmacol.2015 Jan 5;746:308-16. doi: 10.1016/j.ejphar.2014.10.046. Epub 2014 Nov 8.
• Effects of the histamine H1 receptor (H1R) antagonists (antihistamines), promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), citerizine (CTZ), and triprolidine (TRP) on the functional properties of the cloned α7 subunit of the human nicotinic ace
• PMID 25445036

• Update on rupatadine in the management of allergic disorders.

• Mullol J1, Bousquet J, Bachert C, Canonica GW, Giménez-Arnau A, Kowalski ML, Simons FE, Maurer M, Ryan D, Scadding G.
• Allergy.Allergy.2015 Jan;70 Suppl 100:1-24. doi: 10.1111/all.12531.
• In a review of rupatadine published in 2008, the primary focus was on its role as an antihistamine, with a thorough evaluation of its pharmacology and interaction with histamine H1 -receptors. At the time, however, evidence was already emerging of a broader mechanism of action for rupatadine involvi
• PMID 25491409

• Levocetirizine and rupatadine in chronic idiopathic urticaria.

• Johnson M1, Kwatra G, Badyal DK, Thomas EA.
• International journal of dermatology.Int J Dermatol.2014 Dec 17. doi: 10.1111/ijd.12733. [Epub ahead of print]
• BACKGROUND: Chronic idiopathic urticaria (CIU) is a common dermatological condition. Its pathogenesis involves mainly histamine and also other mediators, including platelet-activating factor (PAF) and tumor necrosis factor-α (TNF-α). In the absence of an exact etiology, H1 -antihistaminics are the
• PMID 25521304

Japanese Journal

• The Role of Histamine H1 and H4 Receptors in Atopic Dermatitis: From Basic Research to Clinical Study

• Ohsawa Yusuke,Hirasawa Noriyasu
• Allergology International 63(4), 533-542, 2014
• … Histamine plays important roles in inflammation and nervous irritability in allergic disorders, including atopic dermatitis (AD). … It has been shown to regulate the expression of pruritic factors, such as nerve growth factor and semaphorin 3A, in skin keratinocytes via histamine H1 receptor (H1R). …
• NAID 130004705221

• P7-004　　Histamine inhibits differentiation of skin fibroblasts into myofibroblasts

• 林 琳,澤向 範文,山形 熏,山岡 邦宏,中野 和久,中山田 真吾,田中 良哉
• 日本臨床免疫学会会誌 37(4), 362b-362b, 2014
• … 【Background】Histamine (HA) and TGF-β, major mediators secreted by mast cells are involved in skin inflammation and systemic sclerosis. … 【Results】Expression of H1-receptor (H1R) and H2-receptor (H2R) were detectable in SFBs at both mRNA and protein level. … Interestingly, addition of HA inhibited αSMA expression induced by TGF-β which was antagonized by H1R antagonist but not H2R antagonist. …
• NAID 130004694292

• Vasomotor Effects of Acetylcholine, Bradykinin, Noradrenaline, 5-Hydroxytryptamine, Histamine and Angiotensin II on the Mouse Basilar Artery

• ISLAM Md. Zahorul,WATANABE Yutaka,NGUYEN Ha Thi Thanh,YAMAZAKI-HIMENO Emi,OBI Takeshi,SHIRAISHI Mitsuya,MIYAMOTO Atsushi
• Journal of Veterinary Medical Science 76(10), 1339-1345, 2014
• … We investigated the responsiveness of the mouse basilar artery to acetylcholine (ACh), bradykinin (BK), noradrenaline (NA), 5-hydroxytryptamine (5-HT), histamine (His) and angiotensin (Ang) II in order to characterize the related receptor subtypes in vitro. …
• NAID 130004432214

Related Links

• Histamine H1 Antagonists — NEJM

To the Editor: In their fine review of histamine H1-receptor-antagonist drugs (June 9 issue),1 Simons and Simons do not mention doxepin, a potent and useful H1-receptor antagonist. Although it is not typically placed in this ...

• Histamine H1 receptor (IPR000921) < InterPro < EMBL-EBI

This entry represents the histamine H1 receptor (also known as HH1R), which plays an important role in allergic responses. As a result, a number of selective receptor antagonists have been developed ...

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★リンクテーブル★

リンク元	「H1 blocker」「ヒスタミンH1拮抗薬」「histamine H1 receptor antagonist」
拡張検索	「non-sedating histamine H1 antagonist」
関連記事	「H1」「H」

「H1 blocker」

　　[★]

ヒスタミンH1受容体遮断薬、ヒスタミンH1受容体拮抗薬、H1遮断薬、H1拮抗薬、抗ヒスタミン薬、抗ヒスタミン剤、H1ブロッカー、抗ヒ剤

関

antihistamine、histamine H1 antagonist、histamine H1 receptor antagonist

「ヒスタミンH1拮抗薬」

　　[★]

英

histamine H1 antagonist

関

抗ヒスタミン剤、ヒスタミンH1受容体遮断薬、ヒスタミンH1受容体拮抗薬、ヒスタミンH1遮断薬

「histamine H1 receptor antagonist」

　　[★]

• ヒスタミンH1受容体遮断薬、ヒスタミンH1受容体拮抗薬

関

antihistamine、H1 blocker、histamine H1 antagonist

「non-sedating histamine H1 antagonist」

　　[★]

• 非鎮静型ヒスタミンH1遮断薬、非鎮静型ヒスタミンH1拮抗薬

関

nonsedating histamine H1 antagonist

「H1」

　　[★]

• ヒストンのサブユニット　→　ヒストンH1
• ヒスタミンの受容体 H1受容体
• 癌の分類において肝転移有りを示す。
• 視床束 thalamic fasciculus

関

H, H0, HX

• 胃癌の病期分類に用いられている。
• 肝転移の有無を示す。
• 肝転移を認める。

「H」

　　[★]

• 食道裂孔
• ヒスチジン
• 水素