Dopamine

Pharmacology of Dopamine

1. DOPAMINE PRESENTED BY: AMJAD HUSSAIN M.PHARM (1 ST yr.)

2. Contents Introduction Synthesis Storage & Release Metabolism Dopamine Receptor Mechanism of Action Physiological Action of Dopamine Diseases Associated with Dopamine Parkinson’s Disease Schizophrenia Hyperprolactinemia

3. Dopamine Dopamine (DA) is a major transmitter in basal ganglia, limbic system, CTZ, anterior pituitary, etc. and in a limited manner in the periphery. Dopamine (3,4-dihydroxyphenylethylamine) is the immediate metabolic precursor of norepinephrine and epinephrine. Dopamine (DA) belongs to the family of catecholamines. It is a central neurotransmitter particularly important in the regulation of movement and possesses important intrinsic pharmacological properties.

4. Synthesis Phenylalanine (Phenylalanine hydroxylase) Tyrosine (Tyrosine hydroxylase) DOPA (Dopa decarboxylase) Dopamine (Dopamine Beta-hydroxylase) Noradrenaline (N-methyl transferase) Adrenaline

5. Storage and Release

6. Metabolism

7. Dopamine Receptor Metabotropic G-protein coupled receptors D1 – like family Include subtypes D1 and D5 Activation is coupled to Gs : activates adenyl cyclase inc. cAMP D2 – like family Includes D2, D3 and D4 Activation is coupled to Gi : inhibit adenyl cyclase dec. cAMP Also open K channel & closes Ca influx

8. Presynaptic D2 Autoreceptors D2 receptors located presynaptically function as auto-receptor. When dopamine is not bound to these receptors, they allow its release from the neuron. They provide negative feedback and act as gatekeepers for dopamine.

9. Mechanism of Action

10. Physiological Action of Dopamine Heart Low conc. - stimulate D1 receptors vasodilation dec. BP. High conc. - stimulates beta-receptor inc. cardiac contractility. 2. Kidney Stimulates D1 receptor on proximal tubular cells inc. urination. Activates D1 receptor inc. renin secretion D3 receptor dec. renin secretion

11. 3. Pituitary gland Stimulates pituitary D2 receptors, inhibit prolactin secretion. Inc. growth hormone secretion. Catecholamine release D1 receptor activation promotes release of Adr . & NA. D2 receptor activation inhibits release of Adr . & NA.

12. Parkinson’s Disease Parkinsonism is an extrapyramidal motor disorder characterizes by rigidity, tremor and hypokinesia. Parkinson’s disease (PD) is a progressive degenerative disorder, mostly affecting older people, first described by James Parkinson in 1817. Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and is pathologically caused by the loss of dopamine-producing neurons in the substantia nigra. This results in deficiency of dopamine (DA) in the striatum which controls muscle tone and coordinates movements.

13. Treatment of Parkinson’s Disease Dopamine Precursor Levodopa Dopamine agonist Pramipexole Ropinirole Apomorphine MAO-B inhibitors Selegiline Rasagiline COMT inhibitors Tolcapone Entacapone

14. Levodopa Levodopa is the metabolic precursor of dopamine, it is the single most effective agent in the treatment of PD. Levodopa is itself largely inert, both its therapeutic and adverse effects result from the decarboxylation of levodopa to DA. Levodopa is almost always administered in combination with a peripherally acting inhibitor of aromatic L-amino acid decarboxylase such as carbidopa or benserazide .

15. Schizophrenia Defective dopamine neurotransmission – relative excess of central dopaminergic activity. An increase in DA function in the mesolimbic system and a decreased function in the meso-cortical DA system (D1 predominates). Behavior similar to the behavioral effects of psychostimulants.

16. Role of Dopamine on Prolactin Secretion Inhibits secretion of prolactin by acting on D2 receptors. Treatment of hyperprolactinemia. Ergot derivatives : Bromocriptine, Cabergoline. Non ergot : Quinagolide.

17. Role of Dopamine in Renal System At low dose selectively activates dopamine specific receptors in the renal circulation. Increase blood flow in GFR. Increase in urinary Na+ excretion.

18. References Goodman and Gilman’s : The Pharmacological Basis of Therapeutics, 12 th edition, Chapter – 15,16,22. Tripathi K.D. : Essential of Medical Pharmacology, 8 th edition. Rang H.P. and Dale M.M. : Antipsychotics 7 th edition – 39,45,49,557. https://www.researchgate.net/publication/328997886. http://en.Wikipedia.org/wiki/Dopamine.

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