Prazosin is a sympatholytic medication that is used to treat high blood pressure, anxiety, and posttraumatic stress disorder (PTSD).[2][3] Prazosin is an α1-blocker that acts as an inverse agonist at alpha-1 adrenergic receptors.[4] These receptors are found on vascular smooth muscle, where they are responsible for the vasoconstrictive action of norepinephrine.[3] They are also found throughout the central nervous system.[5] As of 2013, prazosin is off-patent in the US, and the FDA has approved at least one generic manufacturer. Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. When prazosin is started, however, heart rate and contractility go up 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.[6] Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia, blocking alpha-1 receptors, which control constriction of both the prostate and urethra. Although not a first line choice for either hypertension or prostatic hyperplasia, it is a choice for patients who present with both problems concomitantly.[6] There is some evidence that this medication is effective in treating nightmares, mixed results in randomized control trials. Prazosin was, however, shown to be more effective when treating nightmares related to PTSD.[7] The drug is usually recommended for severe stings from Indian Red Scorpion Hottentotta tamulus in Indian Subcontinent.[8][9][10] Common (4–10% frequency) side effects of prazosin include dizziness, headache, drowsiness, lack of energy, weakness, palpitations, and nausea.[2] Less frequent (1–4%) side effects include vomiting, diarrhea, constipation, edema, orthostatic hypotension, dyspnea, syncope, vertigo, depression, nervousness, and rash.[2] A very rare side effect of prazosin is priapism.[2][11] One phenomenon associated with prazosin is known as the "first dose response", in which the side effects of the drug – specifically orthostatic hypotension, dizziness, and drowsiness – are especially pronounced in the first dose.[2] Orthostatic hypotension and syncope are associated with the body's poor ability to control blood pressure without active alpha-adrenergic receptors. Patients on prazosin should be told to rise to stand up slowly, since their poor baroreflex may cause them to faint if their blood pressure is not adequately maintained during standing. The nasal congestion is due to dilation of vessels in the nasal mucosa. Prazosin holds promise as a pharmacologic treatment for alcohol dependence after a 2009 pilot trial[12] was completed. A larger controlled Phase II "Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence" was completed in 2018 and published in the American Journal of Psychiatry.[13] While on the surface Prazosin showed an effect greater than placebo, the confidence intervals in the study vastly exceeded the difference, making the data from this study statistically unreliable.[14] In cancer research, Prazosin triggered apoptosis of glioblastoma‐initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient‐derived glioblastoma‐initiating cells, and increased survival of glioblastoma‐bearing mice. Its activity occurred via a PKCδ‐dependent inhibition of the AKT pathway, which resulted in caspase‐3 activation. So, prazosin is a potential anti‐glioblastoma adjuvant drug.[15] Clinical trials will be initiated to confirm these findings. Understanding the mechanism of action of prazosin may pave the way for the development of new potential treatments also for other cancers, since other cancer cells as well display altered PKCδ signaling, including those in colorectal, pancreatic and liver cancer.[16]