Class (21) Adrenergic Antagonist = Alpha & Beta Adrenergic Antagonist I| Medicinal Chemistry

Download the "Solution Pharmacy" Mobile App to Get All Uploaded Notes, Model Question Papers, Answer Papers, Online Tests and other GPAT Materials - https://play.google.com/store/apps/de... Solution Pharmacy will cover this syllabus of medicinal chemistry 01 for B.Pharmacy 4th semester Unit 02 – (01) Drug acting on the autonomic nervous system (02) Adrenergic neurotransmitters – biosynthesis and catabolism of catecholamine, adrenergic receptors, alpha-adrenergic receptor and beta-adrenergic receptor and the distribution of alpha and beta-adrenergic receptors (03) Sympathomimetic agents structure-activity relation (SAR) of sympathomimetic agents like direct acting – Nor-epinephrine, epinephrine, Phenylephrine, dopamine, methyldopa, clonidine, dobutamine, isoproterenol, terbutaline, salbutamol, bitolterol, naphazoline, oxymetazoline, and xylometazoline. (04) Indirect-acting agents – Hydroxy amphetamine, Pseudoephedrine, propylhexedrine, (05) Agents with a mixed mechanism (06) Adrenergic antagonist – (07) Alpha adrenergic blocker, tolazoline, Phentolamine, Phenoxybenzamine, prazosin, dihydroergotamine, mtyhlesergide. (08) Beta-adrenergic blockers – SAR of beta blockers, Propranolol, Metipranolol, Atenolol, Bisoprolol, esmolol, metoprolol, labetalol, carvedilol ADRENERGIC ANTAGONISTS ALPHA ADRENERGIC BLOCKERS Non-selective alpha - adrenergic antagonists. Eg. Tolazoline and Phentolamine Tolazoline Phentolamine Mechanism of action: Tolazoline and phentolamine have both alpha 1 and alpha 2 blocking activity and produce tachycardia. The blocking action of these agents at presynaptic alpha 2 - receptors, contributes to their cardiac stimulatory effects by enhancing the release of NE. SAR 1. The agents in this class are structurally similar to the imidazoline alpha - agonist and the type of group attached to the imidazoline ring dictates whether it is an agonist or antagonist. 2 For alpha 1 - agonists SAR studies extensive molecular modeling studies have been provided. 3. Phentolamine is more effective alpha- antagonist while the antagonistic action of tolazoline is relatively weak Therapeutic uses: Tolazoline is used to increase blood flow in peripheral vasospastic conditions like Raynaud's syndrome. Tolazoline is used in persistent pulmonary hypertension of the newborn. Phentermine is used to prevent or control hypertensive episodes. Phenoxybenzamine Phenoxybenzamine is the only haloalkyl amine in clinical use at present. Mechanism of action: They are irreversible blockers of alpha - adrenergic receptors. Chemically it is a Beta haloalkylamine produce a long lasting, irreversible a - adrenergic blockade. Initial step involves the formation of an intermediate aziridinium ion which will form reversible complex with the receptor. The positively charge aziridinium ion electrophile then reacts with a nucleophilic group on the receptor resulting in the formation of covalent bond between the drug receptor which will lead to alkylated receptor. Selective a- blockers Prazosin Prazosin is quinazoline alpha 1 - blocker. As a result of its greater alpha 1 - receptor selectively, the quinazoline class of a-blockers exhibits greater clinical utility. Mechanism of action: It has potent alpha 1 - adrenoreceptor blocking activity. It is potent and effective antihypertensive agent and maybe usefully combined with the beta- adrenoreceptor blockers, and thiazide diuretics. SAR 1. Structurally prazosin consists of three components - the quinazolme ring the piperazine ring and acyl moieity 2. The 4- amino group on quinazolin ring is very important for a receptor affinity. 3. The piperazine moiety can be replaced with other heterocyclic moieties (eg piperidine moiety) without loss of affinity. 4. The nature of the acyl group has a significant effect on the pharmacokinetic properties Therapeutic Uses: Used in treatment of hypertension and heart attack. Also help to improve urination flow rate. E-Mail for official and other work - solutionpharmacy@gmail.com #solutionpharmacy #Pharmacologyclass #Pharmacognosyvideos #GPAT