Dopamine AND PD

Introduction Belongs to the family of catecholamine's Dopamine can be further converted into the hormones epinephrine and norepinephrine (also catecholamine’s) Plays a role in regulation of hormones, motor control and learning Found in humans, animals- both vertebrates and invertebrates

Production Produced in the substantia nigra and the ventral tegmental area It is a neurohormone and is released by the hypothalamus

Dopamine Receptors Two classes: D1-like receptor class - D1 (locomotion, reward, etc.) and D5 (Learning and memory) receptor subtypes Activates adenylyl cyclase which leads to increase in concentration of cAMP D2- like receptor class – D2 (locomotion, learning, etc.), D3 (cognition and emotion) and D4 (mostly unknown, possibly cognition) receptor subtypes Inhibits adenylyl cyclase leading to decrease in concentration of cAMP Have similar signaling properties, however have different signal transduction pathways They are G protein-coupled receptors, signaling mediated by interaction with GTP- binding proteins

Dopamine Pharmacology Can be used as an injectable drug Intropin, Dopastat, Revimine used in the treatment of severe hypotension, bradycardia (slow heart rate), circulatory shock, or cardiac arrest Toxicty-LD50-59mg/kg

L-DOPA Levodopa- dopamine precursor to treat Parkinson’s Disease and dopa-responsive Dystonia Typically co-administered with an inhibitor of peripheral decarboxylation Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used These include entacapone and tolcapone.

Psychostimulants Cocaine and substituted amphetamines all increase dopamine neuronal activity These use different mechanisms than L-DOPA Cocaine- dopamine transporter and norepinephrine transporter blocker

Antipsychotic Drugs A range of drugs that reduce dopamine activity have been found useful in the treatment of schizophrenia and other disorders I.E. Valium

Role in Parkinson's Disease Parkinson's Disease has been related to the loss of dopamine secreting neurons in the midbrain called the substantia nigra. The projection of dopamine neurons from the substantia nigra pars compacta to the dorsal striatum plays a significant role in the control of motor function and in learning new motor programs. These neurons are especially vulnerable to damage and when a large fraction of them die, the result is PD. The administration of L-DOPA, the metabolic precursor for dopamine, is a treatment that cannot restore the dopamine cells that have been lost, but causes the remaining cells to produce more dopamine to compensate for what's lost.

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