1. ANTIHISTAMINIC AGENTS PMC-I 5TH SEM UNIT01

ANTIHISTAMINIC AGENTS # MOA#SAR AND STRUCTURE WITH IUPAC NAME@ DRUGS

1. ANTIHISTAMINIC AGENTS Mrs. Sandhya Sujeetkumar Ahire Pharmaceutical Chemistry 10/10/2020 1

2. Point To Be Covered : Introduction Histamine H1 Antagonists H2 Antagonists 10/10/2020 2

3. HISTAMINE Histamine is ( 2-(imidazol-4-yl)ethylamine) Found in all organs and tissue of human body Storage: mast cell ,Basophills It release in body usually in response to tissue injury, Inflammation , allergic or hypersensitivity reaction. 10/10/2020 3

4. Biosynthesis Of Histamine 10/10/2020 4

5. HISTAMINE RECEPTOR RECEPTOR TYPE LOCATION FUNCTION H1 Smooth muscles, CNS tissue Vasodilation, Motion sickness, Bronco constriction H2 Parietal cells Regulate gastric acid secretion H3 Brain Reduce neurotransmitter release, Ach, NE H4 Thymus, small intestine, spleen bone marrow Unkonwn physiological role 10/10/2020 5

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7. PHYSIOLOGICAL ACTION OF HISTAMINE Inflammatory action Allergic reaction Action on cardiovascular systems Itching or pain sensation Headache Peptic ulceration Asthmatic condition 10/10/2020 7

8. MECHANISM OF ACTION FOR ANTI HISTAMINE Block the binding of histamine to its receptor reducing histamine receptor activity on nerves, vascular smooth muscles, Endothelium, mast cells. 10/10/2020 8

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10. 10/10/2020 10 GENERAL STRUCTURE OF ANTIHISTAMINES Streucture requirements Ar’ is aryl – phenyl ,substituted phenyl, hetero aryl groups Ar is aryl or aryl methyl groups X is connecting atom of carbon , oxygen, nitrogen. C-c is usually carbon ethyl chain Nitrogen should be terminal amine and tertiary in nature.

11. ARYL GROUPS: 2 aromatic rings one aryl or heteroaryl and second aralyl or aryl function or an eqivalent embedded in a polycyclic rings Halogen at para position increase the activity 2 ar ring must connected to central carbon, nitrogen or co 2 aryl link may be linked For effectiveness one or moiety should be pyridyl while second substituent on N atom sholud be benzyl gr or substitued. 10/10/2020 11

12. 2. NATURE OF X Simple carbon chain or satured c-o moiety which serves as a spacer gr for required pharmacophore . 3. ALKYL CHAIN Spacer between X and Terminal Nitrogen atom Branching or extension decrease the activity Homologation develop neuroleptic and tricyclic antidepressant from antihistamines C atom attached to N atom branched not affect activity 10/10/2020 12

13. 4. TERMINAL NITROGEN ATOM For maximum activity it should be tertiary amine Terminal nitrogen atom may be part of heterocyclic ring and retains high antihistaminic activity 10/10/2020 13

14. CINICAL USES: Treatment of allergic rhinitis , Angioedema anaphylactic reaction Antiemetic Antitussive Anti histaminic activity Analgesic reaction 10/10/2020 14

15. DIPHENYLHYDRAMINE HCL MOA inverse agonist at H1 receptor Act as an anti muscarinic and an intracellular sodium channel blockers By reversing effect of histamine on the capillaries it can reduce the intensity of allergic symptoms USE antihistaminic, antitussive, antiemetic, sedative 10/10/2020 15 2-( diphenylmethoxy )-N,N- dimethylethanamine

16. TRIPROLIDINE HCL MOA Blocks the action of endogenous histamine which subsequently leads to temporary relief of negative symptoms brought on by histamine. USES Antihistamine 10/10/2020 16

17. PROMETHAZINE HCL MOA: Competitive inhibitor of histamine H1 receptor present on GI tract, uterus, large blood vessels, bronchial muscle. Uses: Allergic rhinitis Allergic conjunctivitis. 10/10/2020 17

18. H2  blockers are a group of medicines that reduce the amount of acid produced by the cells in the lining of the stomach. They are also called 'histamine  H2-receptor antagonists' but are commonly called  H2 blockers . Examples: c imetidine, famotidine, nizatidine and ranitidine H2 RECEPTOR ANTIHISTAMINE 10/10/2020 18

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21. CIMETIDINE MOA Competitive inhibitor of histamine H2 receptor at parietal cell and blocks histamine effect. Result in reduced gastric acid secertion and volume reduction and acidity. USES Gastric and peptic ulcer, duodenal ulcer 10/10/2020 21

22. RANITIDINE MOA Competitive inhibitor of histamine H2 receptor at parietal cell and blocks histamine effect. Result in reduced gastric acid secertion and volume reduction and acidity. Use: Decresase both basal and stimulated HCL acid produced by food, histamine,gastrin,ach Reduce pepsin activiy. 10/10/2020 22

23. 10/10/2020 23 DIMENHYDRINATE Uses: Antiemetic , Antinauseant AMINOALKYL ETHER ANALOGUES

24. 10/10/2020 24 DOXYLAMINES SUCCINATE Uses: Antitussive and decongestants.

25. 10/10/2020 25 DIPHENYLPHYRAMINE HCL Uses: Antiemetic,Antihistaminic,Antitussive

26. 10/10/2020 26 CLEMASTINE FUMARATE Uses: Allergy symptoms,Anaphylactic shock.

27. 10/10/2020 27 BUCLIZINE HCL Uses: Antiemetic

28. 10/10/2020 28 CHLORCYCLIZINE HCL Uses: Antiemetic,Allergic conditions CYCLIC BASIC ANALOGUES

29. 10/10/2020 29 MECLIZINE HCL Uses: Antinauseant,Allergic conditions

30. 10/10/2020 30 CHLORPHENIRAMINE HCL Uses: Allergy symptoms,Rhinitis MONOAMINOALKYL PROPYL ANALOGUE

31. 10/10/2020 31 TRIPROLIDINE HCL Uses: antihistaminic

32. 10/10/2020 32 PHENIRAMINE HCL Uses: H1 antagonist

33. 10/10/2020 33 TRIMEPRAZINE TARTRATE Uses:H1 receptor antagonist TRICYCLIC RING/PHENOTHIAZINES DERIVATIVES

34. 10/10/2020 34 AZATIDINE Uses: Antihistaminic with antiserotonin DIBENZOCYCLOHEPTANES

35. 10/10/2020 35 CYPROHEPTADINE HCL Uses: Appetite stimulator

36. 10/10/2020 36 ASTEMIZOLE Uses: Antiallergic agent NON CLASSICAL DRUGS

37. 10/10/2020 37 CETRIZINE PIPERAZINE DERIVATE LEVOCETRIZINE Uses: Antiallergic

38. 10/10/2020 38 LORATADINE Uses: Long acting non sedating tricyclic antihistaminic drug PYRIDINE AND PIPERIDINE DERV.

39. 10/10/2020 39 CROMOLYAN SODIUM Uses Prophylactic treatment of asthma

40. Draw structure and give nomenclature of any 2 propyl amines antihistamine Explain SAR of H2 antagonist Explain SAR of H1 antagonist with suitable examples Biosynthesis of histamine. Types of histamine receptor 10/10/2020 40 Questioned ask in examination

41. Thank you 10/10/2020 41