Prazosin

Structural formula
General
Non-proprietary name	Prazosin
other names	4-Amino-2- [4- (2-furoyl) -1-piperazinyl] -6,7-dimethoxyquinazoline ( IUPAC )
Molecular formula	C 19 H 21 N 5 O 4 ; C 19 H 21 N 5 O 4 HCl ( hydrochloride ) ;
External identifiers / databases
EC number	242-885-8
ECHA InfoCard	100,038,971
PubChem	4893
ChemSpider	4724
DrugBank	DB00457
Wikidata	Q425296
Drug information
ATC code	C02 CA01
Drug class	Antihypertensive drugs
Mechanism of action	selective α 1 -adrenoceptor - antagonist
properties
Molar mass	383,40 g · mol -1 ; 419.86 g · mol -1 (hydrochloride) ;
Physical state	firmly
Melting point	278-280 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-315-319-335-361
	P: 261-281-305 + 351 + 338
Toxicological data	> 4,000 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Prazosin is a drug from the group of α-adrenoceptor antagonists ( α-blockers ). Like its pharmacological relatives terazosin and doxazosin , it is primarily used to treat arterial hypertension . Prazosin is also used in patients who have Raynaud's syndrome (poor blood circulation in the fingers). It can also be used in benign prostatic hyperplasia (BPH) to improve urine flow; however, more selective drugs with fewer undesirable systemic effects exist for this purpose (e.g. tamsulosin ). Prazosin was patented by Pfizer in 1969 and marketed under the brand name Minipress.

Pharmacological properties

Mechanism of action

Prazosin is a selective antagonist at sympathetic α ₁ -adrenoceptors . It inhibits the contraction of blood vessels mediated by adrenaline and noradrenaline , and thus the increase in blood pressure . The plasma half-life is 2.5–4.0 hours.

Since prazosin (like all α-adrenoceptor antagonists) causes orthostatic complaints relatively often , it is used as the second choice in the treatment of high blood pressure. In addition, its pronounced tolerance development must be taken into account.

Side effects

The following were described as side effects :

Orthostatic complaints can occur especially at the beginning of treatment and when the dose is increased. The first dose can even lead to severe orthostatic hypotension or even loss of consciousness (“phenomenon of the first dose”). Therefore, the dosage should be gradually increased and the dosage increased carefully.

It can also cause tiredness, malaise, weakness, weight gain, liver dysfunction or pancreatitis ; a blocked nose, nosebleed , eye pain or tinnitus ; in individual cases also to allergic reactions such as hives (urticaria), edema or bronchospasm .

Prazosin crosses the placental barrier and is excreted in breast milk. As there are no clinical studies that allow statements about the harmfulness of prazosin during pregnancy or breastfeeding , this substance must not be used in the life situations mentioned.

Interactions

Prazosin increases the effects of other blood pressure lowering medicines.

Further information

Like the structurally related doxazosin mesylate, prazosin hydrochloride exhibits the phenomenon of polymorphism . The individual polymorphic forms show different storage stability with regard to the rate of hydration . The presentation of the solvate-free forms of either of solvents which form no adduct, and by azeotropic distillation of the hydrate with a chlorinated hydrocarbon or by vacuum drying of the crystalline methanol - solvate .

Trade names

Monopreparations

Adversute (D) and a generic (D)

Individual evidence

↑ Entry on prazosin. In: Römpp Online . Georg Thieme Verlag, accessed on July 7, 2014.
↑ ^a ^b Data sheet for Prazosin hydrochloride from Sigma-Aldrich , accessed on November 8, 2016 ( PDF ).
↑ Entry on prazosin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ CJ Estler (Ed.): Pharmacology and Toxicology . 4th edition. Schattauer, Stuttgart a. New York 1995, p. 70.
^ LJ Kostek; Anal. Profiles Drug Subst. 18, 351 (1989); Chem. Abstr. 1990, 145 638.
↑ U.S. 4,092,315 (1978) [1] ; EJ Bianco (Pfizer); Novel crystalline forms of prazosin hydrochloride.
↑ DD 141 674 (1979) [2] ; D. Lehmann, W. Poepel (VEB Dresden); Process for the preparation of the crystalline alpha form of 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4- (2-furoyl) piperazine hydrochloride.
↑ DD 206 671 (1984) [3] ; Lehmann D., Poepel W. (VEB Dresden); Process for the preparation of the crystalline alpha form of 1- (4-amino-6,7-dimethoxy -2-quinazolinyl) -4- (2-furoyl) piperazine hydrochloride.
↑ DE 3 429 415 (1984) [4] ; SOE Lindholm (Fermion); Anhydrous, stable and crystalline form of prazosin hydrochloride and process for its preparation.
↑ EP 237 608 (1986) [5] ; H. Schickaneder, I. Grafe, K.-H. Ahrens (Heumann Pharma); Crystalline, anhydrous delta form of 2- [4- (2-furoyl- (piperazin) -1-yl] -4-amino-6,7-dimethoxyquinazoline hydrochloride and process for its preparation.

[RÖMPP_Online-1] Entry on prazosin. In: Römpp Online . Georg Thieme Verlag, accessed on July 7, 2014.

[Sigma-2] Data sheet for Prazosin hydrochloride from Sigma-Aldrich , accessed on November 8, 2016 ( PDF ).

[ChemIDplus-3] Entry on prazosin in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[4] CJ Estler (Ed.): Pharmacology and Toxicology . 4th edition. Schattauer, Stuttgart a. New York 1995, p. 70.

[5] LJ Kostek; Anal. Profiles Drug Subst. 18, 351 (1989); Chem. Abstr. 1990, 145 638.

[US4092315-6] U.S. 4,092,315 (1978) [1] ; EJ Bianco (Pfizer); Novel crystalline forms of prazosin hydrochloride.

[DD141674-7] DD 141 674 (1979) [2] ; D. Lehmann, W. Poepel (VEB Dresden); Process for the preparation of the crystalline alpha form of 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4- (2-furoyl) piperazine hydrochloride.

[DD206671-8] DD 206 671 (1984) [3] ; Lehmann D., Poepel W. (VEB Dresden); Process for the preparation of the crystalline alpha form of 1- (4-amino-6,7-dimethoxy -2-quinazolinyl) -4- (2-furoyl) piperazine hydrochloride.

[DE3429415-9] DE 3 429 415 (1984) [4] ; SOE Lindholm (Fermion); Anhydrous, stable and crystalline form of prazosin hydrochloride and process for its preparation.

[EP237608-10] EP 237 608 (1986) [5] ; H. Schickaneder, I. Grafe, K.-H. Ahrens (Heumann Pharma); Crystalline, anhydrous delta form of 2- [4- (2-furoyl- (piperazin) -1-yl] -4-amino-6,7-dimethoxyquinazoline hydrochloride and process for its preparation.