Noradrenergic Transmission Overview

Noradrenaline Main neurotransmitter in sympathetic nervous system, released from varicosities on adrenergic neurones. Catecholamines Compounds with a catechol moiety and an amine side-chain, including noradrenaline, adrenaline, and dopamine. Isoproterenol Synthetic derivative of noradrenaline, not naturally present in the body. Tyrosine hydroxylase Enzyme converting l-tyrosine to dihydroxyphenylalanine (dopa), a rate-limiting step in transmitter synthesis. Dopamine ²-hydroxylase Enzyme converting dopamine to noradrenaline, located in synaptic vesicles. Phenylethanolamine N-methyl transferase Enzyme converting noradrenaline to adrenaline in the adrenal medulla. Reserpine Drug blocking transport of noradrenaline and other amines into synaptic vesicles. Guanethidine NA neuron-blocking drug selectively accumulated by noradrenergic nerve terminals. Tyramine Indirectly acting sympathomimetic amine taken up into vesicles in exchange for noradrenaline. Amphetamine Indirectly acting sympathomimetic amine enhancing released NA action and reducing reuptake. Tolerance Development of reduced response to sympathomimetic drugs due to depletion of releasable noradrenaline store. Nicotinic receptor Type of ACh receptor indicated in the peripheral nervous system. Muscarinic receptor Type of ACh receptor indicated in the peripheral nervous system. 1/4 Adrenoceptors Receptors on which NA and Ad act, mediating a wide range of effects. Catechol moiety Benzene ring with two adjacent hydroxyl groups found in catecholamines. Dopa Dihydroxyphenylalanine, precursor to dopamine in transmitter synthesis. Monoamine oxidase Enzyme degrading NA in nerve terminals, blocking uptake 1. Adrenergic transmission Process involving synthesis, storage, release, and action of noradrenaline. Pharmacologically important catecholamines Noradrenaline, adrenaline, dopamine, and isoproterenol. Acetylcholine Transmitter in the peripheral nervous system, acting on nicotinic and muscarinic receptors. Adrenaline Hormone secreted by the adrenal medulla, acting on adrenoceptors. Dopamine Metabolic precursor of noradrenaline and adrenaline, also a neuromodulator in the CNS. Adrenoceptor types Include ±and ²receptors, each with subtypes and specific agonists/antagonists. Tricyclic antidepressants Drugs blocking uptake 1, inhibiting NA reuptake into nerve terminals. Phentolamine Competitive antagonist of ±adrenoceptors, blocking their activation. Propranolol Antagonist of isoprenaline, used to block ²receptors and reduce their activation. Methamphetamine metabolism Processed by P450 enzymes in the liver Renal elimination of amphetamines Approximately 25% excreted through the kidneys Half-life of methamphetamine Approximately 10-12 hours 2/4 Cardiac stimulation by amphetamines Caused by increased extracellular NA concentrations Effects of amphetamines Include tachycardia, chest pain, palpitations, arrhythmias, hypertension, headache, and stroke Inhibition of MAO by high amphetamine At high doses, MAO activity is also inhibdoses ited Ephedrine & Pseudoephedrine origin Derived from Ephedra in Chinese medicine for 3000 years Mixed sympathomimetic action Exhibits both direct and indirect sympathomimetic effects Direct effects of Ephedrine & Pseudoephedrine Weak agonist activity at alpha and beta adrenergic receptors Indirect effects of Ephedrine & Pseudoephedrine Blocks reuptake of NA Sudafed composition Contains Pseudoephedrine for sinus and allergy relief Sudafed PE composition Includes Phenylephrine, an alpha-1 agonist for nasal decongestion Cocaine properties A natural plant alkaloid with indirect sympathomimetic effects in the periphery and CNS Cardiovascular actions of cocaine Result from increased NA in the synapse, stimulating beta-1 receptors and alpha-1 receptors Cocaine's impact on O2 supply Reduces O2 supply due to vasoconstriction of epicardial and resistance vessels Drugs inhibiting NA uptake Inhibit neuronal reuptake of released NA, enhancing sympathetic effects Uptake 1 inhibition Mainly by tricyclic antidepressants like desipramine Enhances sympathetic transmission, Cocaine's effects on sympathetic transcausing tachycardia and increased artemission rial pressure 3/4 Adrenoceptor agonists Include noradrenaline, adrenaline, and selective alpha and beta agonists Clinical uses of adrenoceptor agonists For cardiovascular, respiratory, and miscellaneous indications Alpha-adrenoceptor antagonists Block alpha1 and alpha2 adrenoceptors, with various clinical uses Selective alpha1 antagonists Include prazosin, doxazosin, and terazosin for treating hypertension Beta-adrenoceptor antagonists Act on beta1 and beta2 adrenoceptors, with diverse clinical applications Non-selective beta antagonists Include propranolol, alprenolol, and oxprenolol Selective beta1 antagonists Such as atenolol and nebivolol, with fewer side effects Partial agonist activity of some beta an- Alprenolol and oxprenolol exhibit partial tagonists agonist activity 4/4