15905923020_Diya Bera_Medicinal Chem-II.pptx

15905923020_Diya Bera_Medicinal Chem-II.pptx

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  Presenter Name Continuous Assesement– 1 Topic – SAR of H1 Antagonist (Classical) & A Complete Study of H1 & H2 Antagonists Presented by - Diya Bera Roll No. - 15905923020 Reg. No. - 231590210020(2023-24) Semester – 5th semester Class - 3rd year Course - B.Pharm Suject Code - PT513B Academic Year - 2023-24 Medicinal Chemistry-II Calcutta Institute of Pharmaceutical Technology And Allied Health Sciences Banitabla:Uluberia:Howrah
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  P R ES E N TAT I O N T I T L E 2 Insert photo here 2 / 2 / 2 0 X X
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  Concepts Cover Introduction Histamin Antagonists SARof H1 Antagonist Classification (First & Second Generation) Mechanism of Action Moral Difference of 1st & 2nd generation H1 antagonist Uses Conclusion & References
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  Introduction  Histamine isa -imidazolylethylamine derivative ẞ present in all mammalian tissues.  It was first discovered by SIR HENRY DALE.  Its synthesis from amino acid (L-Histidine) involve of L- Histidine decarboxylase enzyme occurs in mast cells, parietal cells of gastric mucosa, CNS, periphery.  Stored in mast cell and metabilsed by Histamine N- methyl transferase(HMT) & Diamine oxidase.  It functions as an autocoid & one of the mediator involved in the allergic inflammatory responses.  It has an important role in the regulation of gastric acid secretion  Histamin receptor belonging to the family of G-Protein coupled receptors.The sub types of histamine receptors are: H1 H2 H3 H4 2 / 2 / 2 0 X X P R E S E N TAT I O N T I T L E 4
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  2 / 2/ 2 0 X X P R E S E N TAT I O N T I T L E 5 Histamin Antagonists Drugs that block the receptor or histamin that’s called Antihistamines. Began by the discovery of PIPEROXAM. 1. Drugs that inhibits the histumine release. 2. Drugs that inhibits the action of released histamine. a) H1 antagonists(first,second&third generations) b)H2 antagonists c)H3 antagonists d)H4 antagonist 3. Drugs having dual action
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  2 5 /2 6 M e d c h e m Structure Activity Relationship of H1 Antagonist Most of the classic antihistamines are histamine receptor analogue may be described by a substituted ethylamine moiety i.e., GAS.  Aryl group: In the above structure, 1. 1. Ar is aryl (including phenyl & heteroaryl group like 2-pyridyl). 2. 2. Ar' is aryl or aryl methyl group. 3. Some times the two aromatic rings are bridged, which constitutes tricyclic ring derivatives.  The nature of X: Provides the basis of chemical classification of classical anti-histamines- 1. When X = O i.e., GAS = Amino alkylether’s derivatives e.g- Doxylamine 2. When X = N i.e., GAS = Ethylene-diamine’s derivatives e.g- Tripelenamine 3. When X = C i.e., GAS = Mono aminopropyl’s derivative e.g- Pheniramine
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  Structure Activity Relationshipof H1 Antagonist  Nature of Alkylchain: Most of the structures of classical antihistamines contain an ethylene chain. Extension or Branching of this chain results in a less active compound (promethazine is an exception).N-Ar Homologation plays an important role in the development of Neuroleptics & tricyclic antidepressants from anti- histamines.  Nature of Terminal 'N' atom: Terminal 'N' atom should be a 3º amine for the maximum activity. The terminal 'N' may be a part of heterocyclic ring as in Chlorocyclizine, and still retains high antihistaminic activity.
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  Classification of H1Antagonist (First Generation) 2 5 / 2 6 M e d c h e m Amino alkyl ethers: General Structure Ethylenediamine: Propylamine: General Structure General Structure (Saturated)
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  P R ES E N TAT I O N T I T L E 9 Classification of H1 Antagonist (First Generation) 2 / 2 / 2 0 X X Propylamines: General Structure(Unsaturated) Phenothiazine: Piperazine General Structure General Structure
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  P R ES E N TAT I O N T I T L E 1 0 Classification of H1 Antagonist (Second Generation) 2 / 2 / 2 0 X X *These have a relative low affinity for central H, receptors & largely free from sedation. *The 2nd generation drugs have little affinity for muscarnic, adrenergic receptors. *TERFENADINE is a long acting H, antagonist. *FEXOFENADINE is a primary oxidative metabolite of TERFENADINE& does not cross the BBB.
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  2 / 2/ 2 0 X X P R E S E N TAT I O N T I T L E . Mechanism of Action Moral Difference
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  Difference Between ofFirst Generation & Second Generation
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  2 5 /2 6 M e d c h e m Uses of Antihistamins ALLERGIC DISORDERS: They effectively control certain immediate type of allergies like itching. urticaria, seasonal hay fever, allergic conjunctivitis & angioedema of lips eyelids etc., CETIRIZINE have adjuvant role in seasonal asthma. PRURITUS:➤ Antihistamines are first choice of drugs for idiopathic pruritus. COMMON COLD:They do not effect the illness but may afford sympatomatic relief by anticholinergic & sedative actions.As hypnotics eg: diphenhydramine & promethazine. Pruritus
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  2 5 /2 6 M e d c h e m Uses of Antihistamins ➤ As "anti-tussives" Eg: diphenhydramine. ➤ As "anti-emetic" Eg: meclizine ➤ In "parkinsonism" Eg: promethazine, diphenhydramine. ➤ In drug induced "acute dystonias" Eg: diphenhydramine. promethazine. ➤ To treat "motion & morning sickness" Eg: cyclizine, promethazine. ➤ To treat "vertigo" conditions Eg: cinnarizine.
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  Conclusion Histamine is animportant chemical messenger that exhibits significant physiological effects mediated through its receptor. A thorough knowledge of drugs is very much useful to treat the clinical conditions arising due to imbalance of histamine in the body.Antihistamines can be sedating and nonsedating.Older people should avoid sedating antihistamines (first generation).Antihistamine drugs can include pain relievers and decongestants.They often cause drowsiness and nausea.One cannot consume alcohol with antihistamines. 2 5 / 2 6 M e d c h e m
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  Srivastava R, SharmaM, Singh RK. Assessment of adverse drug reactions of antihistamines in a tertiary care hospital. Int J Basic Clin Pharmacol. 2018;7(2):232-6. Nair B, George S, Joseph J. A comparative clinical study of cetirizine and loratadine in seasonal allergic rhinitis. Asian J Pharm Clin Res. 2015;8(4):120-2. Ghosh S, Debnath I, Bhunia S, Hazra S, Nandi S, Mandal SK, Mallya S, Chakraborty S, Shaw AR, Patra S, Khatun R. A review on mechanism of histamine mediated allergic reactions: therapeutic role, safety, and clinical efficacy of cetirizine in modern allergy and other diseases management. Biomed Pharmacol J. 2025;18(1). SK, Sonia SS, Reddy CP, Rao RK, Naidu MUR. Comparative evaluation of H receptor blocking activity ₁ and safety of newer H antagonist mizolastine with loratadine and placebo: a randomized double blind ₁‑ ‑ three way crossover study. ‑ Int J Basic Clin Pharmacol. 2016;5(3):661–675. References
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  Thank you