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Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD).
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Common side effects include dizziness, sleepiness, nausea, and heart palpitations. Prazosin is a non-selective inverse agonist of the α<sub>1</sub>-adrenergic receptors. It is available as a generic medication.
Medical uses
Prazosin is active after taken by mouth and has a minimal effect on cardiac function due to its α<sub>1</sub>-adrenergic receptor selectivity. When prazosin is started, however, heart rate and contractility can increase in order to maintain the pre-treatment blood pressures because the body has reached homeostasis at its abnormally high blood pressure. The blood pressure lowering effect becomes apparent when prazosin is taken for longer periods of time. The heart rate and contractility go back down over time and blood pressure decreases.
The antihypertensive characteristics of prazosin make it a second-line choice for the treatment of high blood pressure.
Prazosin is also useful in treating urinary hesitancy associated with benign prostatic hyperplasia, blocking α<sub>1</sub>-adrenergic receptors, which control constriction of both the prostate and urethra. Although not a first-line choice for either hypertension or benign prostatic hyperplasia, it is a choice for people who present with both problems concomitantly.
Prazosin is used off-label in the treatment of insomnia for its sedative effects. Prazosin is an inverse agonist at α<sub>1</sub>-adrenergic receptors; Prazosin inhibits the output neurons of the noradrenergic pathways in that system, in turn causing sedation.
Adverse effects
Common (4–10% frequency) side effects of prazosin include dizziness, headache, drowsiness, fatigue, weakness, palpitations, and nausea. One phenomenon associated with prazosin is known as the "first-dose response", in which the side effects of the drugspecifically orthostatic hypotension, dizziness, and drowsinessare especially pronounced in the first dose.
Pharmacology
Pharmacodynamics
Prazosin is an α<sub>1</sub>-blocker that acts as a non-selective inverse agonist at α<sub>1</sub>-adrenergic receptors, including of the α<sub>1A</sub>-, α<sub>1B</sub>-, and α<sub>1D</sub>-adrenergic receptor subtypes. It binds to these receptors with affinity (K<sub>i</sub>) values of 0.13 to 1.0 nM for the α<sub>1Α</sub>-adrenergic receptor, 0.06 to 0.62 nM for the α<sub>1B</sub>-adrenergic receptor, and 0.06 to 0.38 nM for the α<sub>1D</sub>-adrenergic receptor. It has much lower affinity for the α<sub>2</sub>-adrenergic receptors (K<sub>i</sub> = 210–5,012 nM for the α<sub>2A</sub>-adrenergic receptor, 13–676 nM for the α<sub>2B</sub>-adrenergic receptor, and 10–257 nM for the α<sub>2C</sub>-adrenergic receptor). The α<sub>1</sub>-adrenergic receptors are found in vascular smooth muscle, where they are responsible for the vasoconstrictive action of norepinephrine. They are also found throughout the central nervous system. α<sub>1</sub>-Adrenergic receptors have additionally been found on immune cells, where catecholamine binding can stimulate and enhance cytokine production. As a repurposed drug, prazosin is being investigated for the prevention of cytokine storm syndrome and complications of COVID-19 where it is thought to decrease cytokine dysregulation.