Dopamine

Dopamine [DOE-pa-meen], the immediate metabolic precursor of norepinephrine, occurs naturally in the CNS in the basal ganglia, where it functions as a neurotransmitter, as well as in the adrenal medulla. Dopamine can activate α- and βadrenergic receptors. For example, at higher doses, it can cause vasoconstriction by activating α1 receptors, whereas at lower doses, it stimulates β1 cardiac receptors.

In addition, D1 and D2 dopaminergic receptors, distinct from the α- and βadrenergic receptors, occur in the peripheral mesenteric and renal vascular beds, where binding of dopamine produces vasodilation. D2 receptors are also found on presynaptic adrenergic neurons, where their activation interferes with norepinephrine release. 

1. Actions:

 a. Cardiovascular: Dopamine exerts a stimulatory effect on the β1 receptors of the heart, having both inotropic and chronotropic effects . At very high doses, dopamine activates α1 receptors on the vasculature, resulting in vasoconstriction.

 b. Renal and visceral: Dopamine dilates renal and splanchnic arterioles by activating dopaminergic receptors, thus increasing blood flow to the kidneys and other viscera. These receptors are not affected by α- or βblocking drugs. Therefore, dopamine is clinically useful in the treatment of shock, in which significant increases in sympathetic activity might compromise renal function. [Note: Similar dopamine receptors are found in the autonomic ganglia and in the CNS.]

 2. Therapeutic uses:

Dopamine is the drug of choice for shock and is given by continuous infusion. It raises the blood pressure by stimulating the β1 receptors on the heart to increase cardiac output, and α1 receptors on blood vessels to increase total peripheral resistance. In addition, it enhances perfusion to the kidney and splanchnic areas, as described above. An increased blood flow to the kidney enhances the glomerular filtration rate and causes sodium diuresis. In this regard, dopamine is far superior to norepinephrine, which diminishes the blood supply to the kidney and may cause renal shutdown. 

3. Adverse effects:

An overdose of dopamine produces the same effects as sympathetic stimulation. Dopamine is rapidly metabolized to homovanillic acid by MAO or COMT, and its adverse effects (nausea, hypertension, arrhythmias) are therefore short-lived.



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