Prazosin

Prazosin

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Systematic (IUPAC) name
[4-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl](2-furyl)methanone
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682245
Licence data	US FDA:link
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	~60%
Protein binding	97%
Biological half-life	2–3 hours
Identifiers
CAS Number	19216-56-9 Y
ATC code	C02CA01 (WHO)
PubChem	CID: 4893
IUPHAR/BPS	503
DrugBank	DB00457 Y
ChemSpider	4724 Y
UNII	XM03YJ541D Y
KEGG	D08411 Y
ChEBI	CHEBI:8364 Y
ChEMBL	CHEMBL2 Y
Chemical data
Formula	C19H21N5O4
Molecular mass	383.401 g/mol
SMILES O=C(N3CCN(c2nc1cc(OC)c(OC)cc1c(n2)N)CC3)c4occc4
InChI InChI=1S/C19H21N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h3-4,9-11H,5-8H2,1-2H3,(H2,20,21,22) Y Key:IENZQIKPVFGBNW-UHFFFAOYSA-N Y
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Prazosin, trade names Minipress, Vasoflex, Lentopres and Hypovase, is a sympatholytic drug used to treat high blood pressure and anxiety, PTSD, and panic disorder. It is an alpha-adrenergic blocker that is specific for the alpha-1 receptors. These receptors are found on vascular smooth muscle, where they are responsible for the vasoconstrictive action of norepinephrine. They are also found throughout the central nervous system. As of 2013, prazosin is off-patent in the US, and the FDA has approved at least one generic manufacturer.

In addition to its alpha-blocking activity, prazosin is an antagonist of the MT₃ receptor (which is not present in humans), with selectivity for this receptor over the MT₁ and MT₂ receptors.

Medical use

Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. However, when prazosin is started, 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.

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.

This medication has shown to be effective in treating severe nightmares in children and people with PTSD symptoms. Veterans have also been treated successfully at Seattle's VA Puget Sound Health Care System (VAPSHCS) for sleep disturbance related to PTSD. Doses are lower for this purpose than for control of blood pressure.

The drug is usually recommended for severe stings from Indian Red Scorpion Hottentotta tamulus in Indian Subcontinent.

Adverse effects

Side effects of prazosin include orthostatic hypotension, syncope, and nasal congestion. The 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.

One phenomenon associated with prazosin is known as the "first dose response", in which the side effects of the drug, especially orthostatic hypotension and fainting, are especially pronounced in the first dose.

One very rare side effect of prazosin is priapism.

Another possible side effect is dreaming while awake or hallucinations of wakefulness while falling asleep on the medication (see oneirophrenia).

Research

Prazosin holds promise as a pharmacologic treatment for alcohol dependence after a 2009 pilot trial was completed. A larger controlled Phase II "Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence" is currently underway.

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. 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.