Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Uploaded byAniketShrivastava14
1,034 views

H1 and H2 antagonist Medicinal Chemistry.pptx

The document provides an extensive overview of histamine, its role in the body, and the classification of antihistamines, including H1 and H2 antagonists. It discusses the mechanisms of action, structure-activity relationships (SAR), and various examples of medications used in allergy treatment and gastric acid inhibition. Key points include the historical development of antihistamines and their specific applications in therapeutic settings.

Education◦
Related topics:
Medicinal Chemistry• B-Pharma• m-pharma•
Download to read offline
H1 and H2 antagonist By- Aniket kumar M. Pharm 1st semester (pharmaceutical chemistry)
CONTENTS HISTAMINE ANTIHISTAMINE RECEPTOR OF ANTIHISTAMINE CLASSIFICATION OF H1 ANTIHISTAMINE MOA H1 ANTAGONIST SAR OF H1 ANTAGONIST H2 ANTAGONIST MOA H2 ANTAGONIST SAR OF H2 ANTAGONIST
Histamine • Histamine is a chemical messenger which are synthesized in the mast cell. • Histamine is present in practically all tissues , with significant amounts in the lungs, skin, blood vessels and GI tract. • Generally histamine are found in the animal tissue , venom of insects bacteria and plant. • Histamine a substance that play a major role in many allergic reaction , dilating blood vessel and making the vessel walls abnormally permeable. • Histamine is a signalling molecule ,sending message b/w cells. It tells stomach cells to make stomach acid and it helps our brain
• English scientists George Barger and Henry H. Dale first isolated histamine from the plant fungus ergot in 1910 and in 1911 they isolated the substance from animal tissues. • Histamine [2 (imidazole -4-yl) ethylamine] which is biosynthesized by decarboxylation of the basic amino acid histidine ,is found all organ and tissue of the human body. • It is formed by the decarboxylation (the removal of a carboxyl group) of the amino acid histidine.
ANTIHISTAMINE • These are the drugs which diminish or antagonize the action of endogenously released histamine in the body . • Antihistamines are generally antagonist of H1 receptor. • These are used for the treatment of allergy and pruritis • Antagonist of H2 receptor are use to inhibit gastric acid secretion (treatment of peptic ulcer). • The human body contains histaminic receptor and are divided into three different types upon their action 1. H1- receptor 2. H2- receptor 3. H3- receptor
Name of receptor Place where it present in our body Antagonist H1-receprtor Smooth muscles ,intestine , bronchi , blood vessels Diphenhydramine mepyramine H2-receptor Gastric parietal cells Cimetidine ranitidine H3 –receptor Neuron , CNS cells Thioperamide RECEPTORS OF ANTIHISTAMINES
H1 RECEPTOR ANTAGONIST • In the year 1933 the first drug Piperoxan invented Bovet & Furnease. This drug can protect the animal from bronchial spasm. The drug is the initiation for the discovery of H1 receptor antagonist. • In the year 1942 , Halpen researched and reported about 24 derivative of ethylene diamine in which Phenbenzamine was found to be most potent and is used the first H1 antagonist used clinically. • H1 antagonists act by competitively inhibiting the effects of histamine at H1 receptor
Mechanism of action of H1 antagonist H1 antagonist
• CLASSIFICATION OF H1 ANTAGONIST H1 ANTAGONIST FIRST GENERATION 1. AMINO ALKYL ETHERS - DIPHENHYDRAMINE 2. ETHYLENEDIAMINE – TRIPELENNAMINE 3.CYCLIC BASIC CHAIN DERIVATIVE- CHLORCYCLIZINE 4.PROPYL AMINE DERIVATIVE- PHENIRAMINE, TRIOLIDINE 5.PHENOTHIAZINE DERIVATIVE- PROMETHAZINE 6. DIBENZO CYCLOHEPTADINE- AZATIDINE 7. MISSCELLANEOUS - ANTAZOLINE SECOND GENERATION 1.PIPERAZINE- CETRIZINE/LEVOCETIRIZINE 2.PIPERIDINES- FEXOFENADINE , LORATADINE/ DESLORATADINE
SAR –H1 RECEPTOR ANTAGONISTS 1. Aryl groups The diaryl substitution is essential for significant H1 affinity. It is present both in first generation and second generation antihistamines. The optimal antihistaminic activity depends on the co-planarity of two aryl substitutions. Active aryl substitutions are as follows: Ar1 is phenyl and hetero aryl group like 2-pyridyl Ar1 -Aryl or aryl methyl group
2. Nature of X Antihistamines with X = carbon (pheniramine series) represents the stereo selective receptor binding to the receptors due to its chirality. The active substitutions of X are as follows: Where X = oxygen (amino alkyl ether analogue) X = nitrogen (ethylene-diamine derivative) X = carbon (mono amino propyl analogue) 3. The Alkyl Chain Most of the antihistamines have ethylene chain, and branching of this chain results in a less active compound.
4. Terminal nitrogen atom: The terminal N-atom should be a 3° amine for maximum activity. The terminal nitrogen may be a part of heterocyclic ring. For example, antazoline and chlorcyclizine, retains high antihistaminic activity. The amino moiety deserves the protonation on interaction with H1 receptor due to the basicity with pka 8.5-10 chlorcyclizine
1st Generation Antihistaminic agents AMINO ALKYL ETHERS DIPHENHYDRAMINE DOXYLAMINE USES- Antiemetic, Antihistamine, Antitussive ,smooth , Muscle Relaxant , sedative Action USES- Cough ,cold , allergic conjuctivites
ETHYLENDIAMINE DERIVATIVE Tripelennamine USES- Allergic rhinitis , Conjunctivitis, Angioedema Uses-Urticaria, conjunctivitis ,hay fever ,antiemetics CYCLIC BASIC CHAIN DERIVATIVE Cyclizine Chlorcyclizine
PROYLAMINE ANALOGS Triprolidine • It is most potent antihistaminic agents. • The activity is mainly due to geometric isomer in which the pyrrolidino - methyl group is trans to the 2pyridyl group. • E isomer showed more activity then Z isomer.
PHENOTHIAZINE DERIVATIVE- PROMETHAZINE • It is the most potent antihistaminic agents • Use in perennial and seasonal allergic rhinitis, allergic conjunctivitis USES-
2nd Generation Antihistaminic agents Fexofenatidine • Used in the treatment of allergy symptoms, such as hay fever , watery eyes, runny nose, itching eyes ,sneezing, and urticaria • Sedative peripheral h1 blocker Loratidine It is long acting ,non sedative tricyclic antihistaminic drug. Used to treat sneezing , runny nose, watery eye, skin rash , itching, and cold or allergy symptoms
SYNTHESIS OF CETIRIZINE
H2 Antagonist • The histamine H2 receptor antagonist act on H2 receptor in the stomach blood vessel and other sites. • They are competitive antagonist of histamine and are fully reversible • H2 antagonist are group of medicines that reduce the amount of acid produced by the cell in the lining of the stomach are commonly called H2 blocker • These products have been approved for the relief of “heartburn” associated with acid indigestion ,and sour stomach. • Drugs – cimetidine, ranitidine, famotidine.
H2 antagonist MECHANISM OF ACTION H2 ANTAGONIST
SAR OF H2 ANTAGONIST • The H2 receptor antagonist were the result of the intentional modification of the histamine structure and deliberate search for a chemically related substance that would act as a competitive inhibitor. Imidazole ring is not the only required ring fir competitive antagonism of histamine H2 receptor
• Other Heterocyclic ring present like Cimetidine ( Imidazole) ,ranitidine (furan), famotidine (Thiazole) etc ,that enhance the potency and selectivity of H2 receptor antagonist can be used. • The ring is terminal nitrogen should be separated by four carbon atom for optimum antagonistic activity. • The terminal nitrogen group should be polar ,non basic substituent for maximal antagonistic activity.
H2 receptor antagonist Cimetidine Famotidine Cimetidine is a stomach acid reflux that is used to treat and prevent certain types of stomach ulcer Used to treat gastroesophageal reflux disease (GERD) and heart burn. Famotidine is used to treat and prevent ulcers in the stomach and intestine. It is used to trat Zollinger- Elison syndrome
RANITIDINE USES- • In the treatment and prevention of stomach and intestinal ulcers • In the treatment of gastritis (stomach inflammation) caused by kidney failure • Used is in the management of acid reflux disease to reduce injury to the oesophagus ( food tube) caused by the upward movement of stomach acid.
REFFERENCES • Eliezer J. Barreiro, Arthur E. Kümmerle, and Carlos A. M. Frag . The Methylation Effect in Medicinal Chemistry. Chemical Reviews 2011, 111 (9) , 5215-5246 • . A. M. Mocking, R. Bosma , S. N. Rahman, E. W. E. Verweij, Daniel A. McNaught-Flores, Henry F. Vischer , Rob Leurs . Molecular Aspects of Histamine Receptors. • Patrick Igel , Stefan Dove, Armin Buschauer . Histamine H4 receptor agonists. Bioorganic & Medicinal Chemistry Letters 2010, 20 (24) , 7191-7199.
H1 and H2 antagonist Medicinal Chemistry.pptx