Antimuscarinics Natural alkaloids i Atropine Prototype hyoscyamine ii

Antimuscarinics Natural alkaloids i) Atropine (Prototype) (± hyoscyamine) ii) Scopolamine (l- hyoscine) � Semisynthetic derivatives i) Homatropine ii) Atropine iii) Hyoscine iv) Anisotropine v) Benztropine vi) Ipratropium bromide vii) Tiotropium bromide � • Synthetic derivatives Tertiary Amines Quaternary der. i. Biperidine i. Propantheline ii. Cyclopentolate ii. Methantheline iii. Eucatropine iii. Glycopyrrolate iv. Telenzepine iv. Oxyphenonium v. Oxybutinin v. Isopropamide vi. Pirenzipine vi. Pipenzolate

• Prototype Structure Where A, B = Bulky groups e. g: - Cycloalkyl aromatic C = H, OH or carboxamide

i) Substituent A & B Contains at least one aromatic moiety capable of vander waals interactions. ii) Substituent C May be Hydroxyl or Carboxamide moiety.

� Cationic head Loss of cationic head leads the drug to act as a antagonist. � The hydroxyl group Enhances anti-muscarinic properties. � The esteratic group Contributing feature for effective binding. � Cyclic substitution One cyclic substituent is necessary in structure of anti-cholinergics.

i) Atropine Atropa belladona

� SAR I. II. Piperidine ring in a chair conformation. Two stereomeric forms tropine & pseudotropine.

III. (-) Hyoscyamine is more potent than (+) Hyoscyamine Racemate Atropine has intermittent activity.

� Mechanism of Action Inhibits actions of M 1, M 2 & M 3. Most active in case of exogenously administered choline esters. � Therapeutic use i. Motion sickness ii. Eye iii. CVS system ( A goes with B) iv. Respiratory tract � ROA i. m, i. v, oral & ophthalmic.

II. Scopolamine l-hyoscine formed by by combination of aromatic acid- tropic acid & scopine. � MOA: On the cortex or vestibular apparatus.

i) Homatropine methylbromide It is 3α-hydroxy-8 -methyl-1αH, 5αHtropanium.

� MOA Inhibits muscarinic actions of Ach therefore reduces motility and secretory activity of GI system. � Th. use In treatment of peptic ulcers, gastric ulcers & duodenal ulcers. � ROA Oral & Ophthalmic route.

ii) Ipratropium bromide It’s a quaternary ammonium derivative of atropine. � MOA ‘ipr. Atropium’ Atropine is buried within ipratropium. So acts like atropine

� Th. Use Maintenance treatment of bronchospasm associated with COPD. � ROA Inhalation in aerosol or by nasal route in solution form.

i) Cyclopentolate Hydrochloride It’s a tertiary amine derivative of cyclopentaneacetate hydrochloride.

� MOA blocks muscarinic receptors & produces mydriasis. Cyclopentolate= ½(Atropine Х Antispasmodic) � Th. Use To produce mydriasis & cycloplegia for diagnostic purpose. � ROA Ophthalmic route.

i) � Propantheline bromide MOA Potent anti-cholinergic inhibits sympathetic & parasympathetic systems.

� Th. Use In gastritis & peptic ulcers.