Dopamine

DOPAMINE

INTRODUCTION:

• Dopamine belongs to family of catecholamines.
• Major neurotransmitter in substantia nigra.
• Generates slow IPSP in ANS.
• Significant role in learning, goal-directed behavior, regulation of hormones & motor control.

DOPAMINE RECEPTORS:

• Metabotropic G-protein coupled receptors

D1 – like family:

• Includes subtypes D1 & D5.
• Activation is coupled to Gs.
• Activates adenylyl cylcase resulting in increased cAMP concentration.

D2 – like family:

• Includes D2, D3 & D4.
• Activation is coupled to Gi.
• Inhibits adenylyl cyclase leading to decreased cAMP concentration.
• Also open K channels & closes Ca influx.
• Dopamine receptor with inhibitory action is D2.

DOPAMINERGIC PATHWAYS:

• Mesolimbic Pathway.
• Mesocortical Pathway.
• Nigrostriatal Pathway:
• Efferent fiber bundle of substantia nigra transmits dopamine to Corpus striatum.
• Tuberoinfundibular Pathway.
• Incertohypothalamic Pathway.
• Medullary Periventricular.
• Retinal.

DRUGS MODIFYING DOPAMINERGIC TRANSMISSION:

USES:

Schizophrenia:

• Defective dopamine neurotransmission – relative excess of central dopaminergic activity.
• An increase in DA function in mesolimbic system and decreased function in mesocortical DA systems (D1 predominates).
• Behavior similar to behavioral effects of psychostimulants.

Parkinson’s Disease

• Parkinson’s sufferers have low levels of dopamine.
• L-dopa raises DA activity.
• People with Parkinson’s develop schizophrenic symptoms if they take too much L-dopa.
• Treatment strategy includes –
• Increasing dopamine levels, nerve grafting with dopamine containing cells and deep brain stimulation.
• Bromocriptine,Ropinerole & Pramipexole are dopaminergic agonists used for parkinsonism.

 Other motor disorders:

• Huntington’s disease
• Tourrette’s syndrome
• D2 Blockers – Chlorpromazine & Haloperidol.

Attention deficit hyperactivity disorder

• Altered dopamine neurotransmission is implicated in attention deficit hyperactivity disorder (ADHD).
• Most effective therapeutic agents for ADHD are psychostimulants.
• Methylphenidate & Amphetamine
• Increase both dopamine & norepinephrine levels in brain.

Addiction:

• Psychostimulants such as Cocaine & Amphetamine.
• By altering dopamine activity in brain.
• Inhibits prolactin secretion by acting on D2 receptors.

Role in renal system:

• Dopamine at 1-2 Microgram/ Kg/ min produces renal vasodilatation by acting on D1 receptors.
• Preferred in treatment of shock with oliguric renal failure.
• Effectiveness attributed to renal vasodilatory effect.
• Selectively activates dopamine specific receptors in the renal and splanchnic circulation.
• Increase renal blood flow.
• Increases GFR.
• Increases urinary Na excretion.
• Effect of dopamine on kidney is blocked by Haloperidol.
• Heart and Vasculature:
• Causes vasoconstriction.
• At low concentrations, circulating DA primarily stimulates vascular D1 receptors, causing vasodilation and reducing cardiac afterload.
• Activates adrenergic receptors to further increase cardiac contractility.
• The net result is a decrease in blood pressure and an increase in cardiac contractility.
• Drug most useful in cardiogenic shock.
• Anti-insulin
• Analgesic.
• Role in apoptosis.
• Memory.
• Immune.

Exam Question

• The strategy for therapy for dopamine deficiency in the substantia nigra of individuals with Parkinson’s disease is indicated by provision of metabolites in the tyrosine pathway.
• Neurotransmitter related to schizophrenia pathology is dopamine.
• The efferent fiber bundle of the substantia nigra transmits dopamine to Corpus striatum.
• Dopamine is the major neurotransmitter in substantia nigra.
• Slow IPSP in autonomic is generated by dopamine.
• Adrenaline, noradrenaline and dopamine act through seven pass receptor.
• Dopamine shows positive ionotropic effect.
• Dopamine improves renal perfusion.
• Dopamine causes vasoconstriction. 
• Effect of dopamine on kidney is blocked by Haloperidol.
• Dopamine is preferred in treatment of shock because of renal vasodilatory effect.
• Prolactin secretion will be inhibited by dopamine.
• Bromocriptine,Ropinerole & Pramipexole are dopaminergic agonists used for parkinsonism.
• Dopamine neurotransmitter is depleted in Parkinson’s disease
• Drug most useful in cardiogenic shock is dopamine.
• Dopamine is preferred over dobutamne in treatment of renal shock because of renal vasodilatory effect.
• Anti-psychotic drugs act through Dopamine D4 receptor blockade.
• Dopamine at 1-2 Microgram/ Kg/ min produces renal vasodilatation.
• Dopamine receptor with inhibitory action is D2.