Prazosin

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Prazosin
Systematic (IUPAC) name
2-[4-(2-furoyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
Clinical data
Trade namesMinipress
AHFS/Drugs.commonograph
MedlinePlusa682245
Pregnancy cat. ?
Legal statusPOM (UK)
RoutesOral
Pharmacokinetic data
Bioavailability~60%
Protein binding97%
Half-life2–3 hours
Identifiers
CAS number19216-56-9 YesY
ATC codeC02CA01
PubChemCID 4893
IUPHAR ligand503
DrugBankDB00457
ChemSpider4724 YesY
UNIIXM03YJ541D YesY
KEGGD08411 YesY
ChEBICHEBI:8364 YesY
ChEMBLCHEMBL2 YesY
Chemical data
FormulaC19H21N5O4 
Mol. mass383.401 g/mol
 YesY (what is this?)  (verify)
 
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Prazosin
Systematic (IUPAC) name
2-[4-(2-furoyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
Clinical data
Trade namesMinipress
AHFS/Drugs.commonograph
MedlinePlusa682245
Pregnancy cat. ?
Legal statusPOM (UK)
RoutesOral
Pharmacokinetic data
Bioavailability~60%
Protein binding97%
Half-life2–3 hours
Identifiers
CAS number19216-56-9 YesY
ATC codeC02CA01
PubChemCID 4893
IUPHAR ligand503
DrugBankDB00457
ChemSpider4724 YesY
UNIIXM03YJ541D YesY
KEGGD08411 YesY
ChEBICHEBI:8364 YesY
ChEMBLCHEMBL2 YesY
Chemical data
FormulaC19H21N5O4 
Mol. mass383.401 g/mol
 YesY (what is this?)  (verify)

Prazosin, trade names Minipress, Vasoflex, Pressin 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.[1] 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.[2]

Medical use[edit]

Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. However, when prazosin is initially 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.[3]

Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia, blocking alpha-1 receptors, which control constriction of both the prostate and ureters. Although not a first line choice for either hypertension or prostatic hyperplasia, it is a choice for patients who present with both problems concomitantly.[3]

This medication has shown to be effective in treating severe nightmares in children and people with PTSD symptoms.[4] 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.[4]

Prazosin holds promise as a pharmacologic treatment for alcohol dependence after a 2009 pilot trial l was completed. A larger controlled Phase II trial "Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence" is currently underway, set to be completed November 2013.

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

Adverse effects[edit]

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 not to stand up too quickly, 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.[5] Another possible side effect is dreaming while awake or hallucinations of wakefulness while falling asleep on the medication (see oneirophrenia).[citation needed]

Chemistry[edit]

Prazosin can be synthesized from 2-amino-4,5-dimethoxybenzoic acid.[6] Reaction with sodium cyanate leads heterocyclization into 2,4-dihydroxy-6,7-dimethoxyquinazoline. Substituting hydroxyl groups of this compound with chlorine atoms by reaction with thionyl chloride, or a mixture of phosphorus oxychloride with phosphorus pentachloride gives 2,4-dichloro-6,7-dimethoxyquinazoline. Upon subsequent reaction with ammonia, the chlorine atom at C4 of the pyrimidine ring is replaced with an amino group, which leads to the formation of 4-amino-2-chloro-6,7-dimethoxyquinazoline. Introducing this into a reaction with 1-(2-furoyl)piperazine gives prazosin.

Prazosin synthesis.png

References[edit]

  1. ^ Day, H. E.; Campeau, S.; Watson Jr, S. J.; Akil, H. (1997). "Distribution of alpha 1a-, alpha 1b- and alpha 1d-adrenergic receptor mRNA in the rat brain and spinal cord". Journal of chemical neuroanatomy 13 (2): 115–139. doi:10.1016/S0891-0618(97)00042-2. PMID 9285356.  edit
  2. ^ Yu CX, Zhu CB, Xu SF, Cao XD, Wu GC (March 2000). "Selective MT(2) melatonin receptor antagonist blocks melatonin-induced antinociception in rats". Neuroscience Letters 282 (3): 161–4. PMID 10717416. 
  3. ^ a b Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 13. ISBN 1-59541-101-1. 
  4. ^ a b "Drug Helps PTSD Nightmares" (Press release). Department of Veteran Affairs. March 30, 2008. Retrieved 2009-03-16. 
  5. ^ Bhalla AK, Hoffbrand BI, Phatak PS, Reuben SR (October 1979). "Prazosin and priapism". Br Med J 2 (6197): 1039. doi:10.1136/bmj.2.6197.1039. PMC 1596841. PMID 519276. 
  6. ^ E. Honkanen, A. Pippuri, P. Kairisalo, M. Koivisto, S. Tuorni, J. Heterocycl. Chem., 17, 797(1980)