Dopamin ( A short Pharmacological review)

As a biogenic amine, 3, 4-dihydroxyphenylethylamine, dopamine belongs to a group of substances produced in the organism by de-carboxylation of amino acids. Besides dopamine and nor-epinephrine formed from it, this group includes many other messenger molecules such as histamine, serotonin, and γ-amino butyric acid.

Dopamine actions and its pharmacological implications.

In the CNS, dopamine serves as a neuro-mediator. Dopamine receptors are also present in the periphery. Neuronally released dopamine can interact with various receptor subtypes, all of which are coupled to G-proteins.

Two groupings can be distinguished:

• The family of D1-like receptors (comprising subtypes D1 and D5)
• The family of D2-like receptors (comprising subtypes D2, D3, and D4).

The subtypes differ in their signal transduction pathways. Thus, synthesis of cAMP is stimulated by D1-like receptors but inhibited by D2-like receptors.

Released dopamine can be reutilized by neuronal reuptake and re storage in vesicles or can be catabolized like other endogenous catecholamines by the enzymes MAO and COMT.

Various drugs are employed therapeutically to influence dopaminergic signal transmission.

• Antiparkinsonian agents:

In Parkinson disease, nigrostriatal dopamine neurons degenerate. To compensate for the lack of dopamine, use is made of L-dopa as the dopamine precursor and of D2 receptor agonists.

• Prolactin inhibitors:

Dopamine released from hypothalamic neurosecretory nerve cells inhibits the secretion of prolactin from the adenohypophysis. Prolactin promotes production of breast milk during the actuation period; moreover it inhibits the secretion of gonadorelin.

D2 receptor agonists prevent prolactin secretion and can be used for weaning and the treatment of female infertility resulting from hyperprolactinemia.

The D2 agonists differ in their duration of action and, hence, their dosing interval; e. g.

• Bromocriptine 3 times daily,
• Quinagolide once daily,
• Cabergoline once to twice weekly etc

• Antiemetics:

Stimulation of dopamine receptors in the area postrema can elicit vomiting. D2 receptor antagonists such as metoclopramide and domperidone are used as antiemetics.

In addition they promote gastric emptying.

• Neuroleptics:

Various CNS-permeant drugs that exert a therapeutic action in schizophrenia display antagonist properties at D2 receptors; e. g., the phenothiazines and butyrophenone neuroleptics.

Dopamine as a therapeutic agent

• When given by infusion, dopamine causes a dilation of renal and splanchnic arteries that result from stimulation of D1 receptors. This lowers cardiac after load and augments renal blood flow, effects that are exploited in the treatment of cardiogenic shock. Because of the close structural relationship between dopamine and nor epinephrine, it is easy to understand why, at progressively higher doses, dopamine is capable of activating β1-adrenoceptors and finally α1-receptors.
• In particular, α-mediated vasoconstriction would be therapeutically undesirable (symbolized by red warning sign). Apomorphine is a dopamine agonist with a variegated pattern of usage. Given parenterally as an emetic agent to aid elimination of orally ingested poisons, it is not without hazards (hypotension, respiratory depression). In kinetic motor disturbances, it is a backup drug.
• Taken orally, it supposedly is beneficial in erectile dysfunction.

Source : Color Atlas of  Pharmacology (3rd edition,) revised and expanded
Heinz Lüllmann, M.D.

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