WordNet

a complex consisting of an organic base in association with hydrogen chloride
antihypertensive drug (trade name Minipress) (同)Minipress

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/02/24 04:35:27」(JST)

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Prazosin, trade names Minipress, Vasoflex, Lentopres and Hypovase, is a sympatholytic drug used to treat high blood pressure, anxiety, and posttraumatic stress disorder (PTSD).^[2]^[3] It is an α₁-blocker which 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.

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.^[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]

This medication has shown to be effective in treating severe nightmares in children and people with PTSD symptoms.^[7] 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.^[7]

The drug is usually recommended for severe stings from Indian Red Scorpion Hottentotta tamulus in Indian Subcontinent.^[8]^[9]^[10]

Adverse effects

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.

Research

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" is currently underway.^[13]

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.^[14] 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.^[15]

References

^ Packer M, Meller J, Gorlin R, Herman MV (1979). "Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure". Circulation. 59 (3): 531–9. doi:10.1161/01.cir.59.3.531. PMID 761333.
^ ^a ^b ^c ^d ^e "Minipress Prescribing Information" (PDF). United States Food and Drug Administration. Pfizer. February 2015. Retrieved 3 June 2016.
^ ^a ^b "Prazosin: Clinical data". IUPHAR. International Union of Basic and Clinical Pharmacology. Retrieved 3 June 2016. This sympatholytic drug is used in the treatment of hypertension, anxiety and post-traumatic stress disorder. ... Antagonist of alpha-1 adrenoceptors on vascular smooth muscle, thereby inhibiting the vasoconstrictor effect of circulating and locally-released adrenaline and noradrenaline, resulting in peripheral vasodilation.
^ "Prazosin: Biological activity". IUPHAR. International Union of Basic and Clinical Pharmacology. Retrieved 3 June 2016.
^ 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.
^ ^a ^b Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 13. ISBN 1-59541-101-1.
^ ^a ^b "Drug Helps PTSD Nightmares" (PDF) (Press release). VA Research Currents. April 2007. Retrieved 2014-01-06.
^ Bawaskar, H.S. & P.H. Bawaskar (2008). "Scorpion sting: A study of clinical manifestations and treatment regimes" (PDF). Current Science. 95 (9): 1337–1341. Retrieved 14 April 2010.
^ Bawaskar, H.S. & P.H. Bawaskar (2007). "Utility of scorpion anti-venin vs. prazosin in the management of severe Mesobuthus tamulus (Indian red scorpion) envenoming at rural settings" (PDF). JAPI. 55: 14–21. Retrieved 14 April 2010.
^ Pandi, K.; Krishnamurthy, S.; Srinivasaraghavan, R.; Mahadevan, S. (18 February 2014). "Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial". Archives of Disease in Childhood. 99 (6): 575–580. doi:10.1136/archdischild-2013-305483.
^ 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.
^ Simpson, TL; Saxon, AJ; Meredith, CW; Malte, CA; McBride, B; Ferguson, LC; Gross, CA; Hart, KL; Raskind, M (2009). "A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence". Alcoholism: Clinical and Experimental Research. 33 (2): 255–63. doi:10.1111/j.1530-0277.2008.00807.x. PMID 18945226.
^ Study of the Medication Prazosin for Alcohol Dependence
^ S. Assad Kahn, S. L. Costa, S. Gholamin, R. T. Nitta, L. G. Dubois, M. Feve, M. Zeniou, P. L. C. Coelho, E. El-Habr, J. Cadusseau, P. Varlet, S. S. Mitra, B. Devaux, M.-C. Kilhoffer, S. H. Cheshier, V. Moura-Neto, J. Haiech, M.-P. Junier, H. Chneiweiss. (2016). The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKC -dependent inhibition of the AKT pathway. EMBO Molecular Medicine, doi:10.15252/emmm.201505421
^ Recycling an anti-hypertensive agent to fight brain tumors. ScienceDaily 21 April 2016

UpToDate Contents

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1. 成人における心的外傷後ストレス障害の薬物療法 pharmacotherapy for posttraumatic stress disorder in adults
2. 物質使用障害および不安関連障害を併発した成人の治療 treatment of co occurring substance use disorder and anxiety related disorders in adults
3. 初期治療に抵抗性を示したレイノー現象の治療 treatment of the raynaud phenomenon resistant to initial therapy
4. レイノー現象に対する初期治療 initial treatment of the raynaud phenomenon
5. 降圧剤と脂質 antihypertensive drugs and lipids

English Journal

Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.

Palotai M1, Telegdy G2, Tanaka M3, Bagosi Z1, Jászberényi M1.
Behavioural brain research.Behav Brain Res.2014 Nov 1;274:264-9. doi: 10.1016/j.bbr.2014.08.007. Epub 2014 Aug 10.
Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlyin
PMID 25116251

Excitatory drive onto dopaminergic neurons in the rostral linear nucleus is enhanced by norepinephrine in an α1 adrenergic receptor-dependent manner.

Williams MA1, Li C2, Kash TL3, Matthews RT4, Winder DG5.
Neuropharmacology.Neuropharmacology.2014 Nov;86:116-24. doi: 10.1016/j.neuropharm.2014.07.001. Epub 2014 Jul 10.
Dopaminergic innervation of the extended amygdala regulates anxiety-like behavior and stress responsivity. A portion of this dopamine input arises from dopamine neurons located in the ventral lateral periaqueductal gray (vlPAG) and rostral (RLi) and caudal linear nuclei of the raphe (CLi). These neu
PMID 25018040

Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats.

Drummond ES1, Dawson LF1, Finch PM1, Li W2, Guo TZ3, Kingery WS3, Drummond PD4.
Neuroscience.Neuroscience.2014 Oct 3. pii: S0306-4522(14)00797-0. doi: 10.1016/j.neuroscience.2014.09.046. [Epub ahead of print]
In certain forms of nerve injury and inflammation, noradrenaline augments pain via actions on up-regulated α1-adrenoceptors (α1-ARs). The aim of this study was to use immunohistochemistry to examine α1-AR expression on peripheral neurons, cutaneous blood vessels and keratinocytes after distal tib
PMID 25267387

Japanese Journal

反復性尿路感染症と遺尿症を合併し, 左異所性尿管瘤, 尿道狭窄および左低形成腎が認められた1女児例

植村篤実,平松美佐子,秋田泰之
日本小児腎臓病学会雑誌 = Japanese journal of pediatric nephrology 21(2), 199-202, 2008-11-15
… 不安定膀胱としてdistigmine bromideとprazosin hydrochlorideを使用したところ昼間尿失禁は消失した。 …
NAID 10025170560

シロドシン(KMD-3213)のα_1-アドレナリン受容体サブタイプ選択性及び臓器特異性(<特集>シロドシン)

立道聡,小林久美,前澤綾香,小林護,山崎芳伸,柴田信男
藥學雜誌 126(増刊号), 209-216, 2006-03-01
… In the receptor-binding study, a replacement experiment using [^3H]-prazosin was conducted using the membrane fraction of mouse-derived LM (tk-) cells in which each of three human α_1-AR subtypes was expressed. … Using the Magnus method, we studied the inhibitory effect of silodosin on noradrenaline-induced contraction, and compared it with those of tamsulosin hydrochloride, naftopidil and prazosin hydrochloride. …
NAID 110006154997

「プラゾシン」

Prazosin
Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a682245
License data	US FDA: Prazosin;
Routes of; administration	Oral
ATC code	C02CA01 (WHO);
Legal status
Legal status	UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	~60%
Protein binding	97%
Onset of action	30–90 minutes
Biological half-life	2–3 hours
Identifiers
	IUPAC name [4-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl](2-furyl)methanone;
CAS Number	19216-56-9 ;
PubChem CID	4893;
IUPHAR/BPS	503;
DrugBank	DB00457 ;
ChemSpider	4724 ;
UNII	XM03YJ541D;
KEGG	D08411 ;
ChEBI	CHEBI:8364 ;
ChEMBL	CHEMBL2 ;
ECHA InfoCard	100.038.971
Chemical and physical data
Formula	C19H21N5O4
Molar mass	383.401 g/mol
3D model (Jmol)	Interactive image;
	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) ; Key:IENZQIKPVFGBNW-UHFFFAOYSA-N ;
(verify)

　　[★]

英: prazosin
化: 塩酸プラゾシン prazosin hydrochloride
商: ミニプレス Minipress、ダウナット
関: αアドレナリン受容体遮断薬、アドレナリン受容体

GOO. 269.

分類

αアドレナリン受容体遮断薬

選択的α1受容体拮抗薬

薬理作用

末梢動脈の拡張→末梢血管抵抗↓→血圧↓(α₁受容体遮断による) (SPC.249)
動静脈に働き末梢血管抵抗を減少させ、静脈還流量を低下させる (GOO.269)
心臓の前負荷を減らす。心拍出量と心拍数には影響を与えない (GOO.269)
反射性頻脈が少ない。(他の血管拡張薬では心拍数↑。hydralazine) (GOO.269)

→前負荷減少、選択的α1遮断、さらには中枢神経に働いて、交感神経系の出力を抑制しているのかも (GOO.269)

ホスホジエステラーゼ阻害

ミニプレス

プラゾシンは高血圧自然発症ラット、腎性高血圧ラット、DOCA高血圧ラットのいずれにおいても優れた降圧作用が認められている。
プラゾシンの降圧作用はα受容体を遮断することにより末梢血管を拡張させ、その抵抗を減少させることによるが、従来のα遮断薬と異なり、シナプス後α受容体を選択的に遮断し、シナプス前α受容体にはほとんど作用しない。このためシナプス前α受容体を介するノルアドレナリン放出の負のフィードバック機構を抑制せず、過剰のノルアドレナリン放出をおこさないことがin vitroにおけるウサギ肺動脈の試験で認められている。シナプス後α受容体に対するプラゾシンの選択的な作用は本態性高血圧症患者に反射性頻脈をほとんどきたさないこと、レニン活性に及ぼす影響が少ないこと、長期連用による耐性発現がみられないこと10)などの特性に関連するものと考えられている。

適応

抗高血圧薬として(SPC.249)
前立腺肥大症での排尿障害
腎機能低下例にも適応可能
静脈系の拡張作用を持つので、心臓の前負荷・後負荷を軽減し、心不全にも適応可

副作用

first-dose phenomenone (SPC.249)
起立性低血圧 postural hypotension syncope

老人に多い

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[pmid761333-1] Packer M, Meller J, Gorlin R, Herman MV (1979). "Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure". Circulation. 59 (3): 531–9. doi:10.1161/01.cir.59.3.531. PMID 761333.

[Minipress_Rx_Info-2] "Minipress Prescribing Information" (PDF). United States Food and Drug Administration. Pfizer. February 2015. Retrieved 3 June 2016.

[Prazosin_clinical_data-3] "Prazosin: Clinical data". IUPHAR. International Union of Basic and Clinical Pharmacology. Retrieved 3 June 2016. This sympatholytic drug is used in the treatment of hypertension, anxiety and post-traumatic stress disorder. ... Antagonist of alpha-1 adrenoceptors on vascular smooth muscle, thereby inhibiting the vasoconstrictor effect of circulating and locally-released adrenaline and noradrenaline, resulting in peripheral vasodilation.

[Prazosin_biological_activity-4] "Prazosin: Biological activity". IUPHAR. International Union of Basic and Clinical Pharmacology. Retrieved 3 June 2016.

[pmid9285356-5] 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.

[pharmnemonics-6] Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 13. ISBN 1-59541-101-1.

[Drug_helps_PTSD-7] "Drug Helps PTSD Nightmares" (PDF) (Press release). VA Research Currents. April 2007. Retrieved 2014-01-06.

[bawaskar.26bawaskar2008-8] Bawaskar, H.S. & P.H. Bawaskar (2008). "Scorpion sting: A study of clinical manifestations and treatment regimes" (PDF). Current Science. 95 (9): 1337–1341. Retrieved 14 April 2010.

[bawaskar.26bawaskar2007-9] Bawaskar, H.S. & P.H. Bawaskar (2007). "Utility of scorpion anti-venin vs. prazosin in the management of severe Mesobuthus tamulus (Indian red scorpion) envenoming at rural settings" (PDF). JAPI. 55: 14–21. Retrieved 14 April 2010.

[10] Pandi, K.; Krishnamurthy, S.; Srinivasaraghavan, R.; Mahadevan, S. (18 February 2014). "Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial". Archives of Disease in Childhood. 99 (6): 575–580. doi:10.1136/archdischild-2013-305483.

[pmid519276-11] 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.

[12] Simpson, TL; Saxon, AJ; Meredith, CW; Malte, CA; McBride, B; Ferguson, LC; Gross, CA; Hart, KL; Raskind, M (2009). "A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence". Alcoholism: Clinical and Experimental Research. 33 (2): 255–63. doi:10.1111/j.1530-0277.2008.00807.x. PMID 18945226.

[13] Study of the Medication Prazosin for Alcohol Dependence

[14] S. Assad Kahn, S. L. Costa, S. Gholamin, R. T. Nitta, L. G. Dubois, M. Feve, M. Zeniou, P. L. C. Coelho, E. El-Habr, J. Cadusseau, P. Varlet, S. S. Mitra, B. Devaux, M.-C. Kilhoffer, S. H. Cheshier, V. Moura-Neto, J. Haiech, M.-P. Junier, H. Chneiweiss. (2016). The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKC -dependent inhibition of the AKT pathway. EMBO Molecular Medicine, doi:10.15252/emmm.201505421

[15] Recycling an anti-hypertensive agent to fight brain tumors. ScienceDaily 21 April 2016

v t e Anxiolytics (N05B)

5-HT_1A agonists	Buspirone Tandospirone

GABA_AR PAMs	Benzodiazepines: Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam^# Ethyl loflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam^# Medazepam Nordazepam Oxazepam Pinazepam Prazepam Others: Alpidem^‡ Barbiturates Carbamates Chlormezanone^‡ Ethanol Etifoxine; Herbs: Kava Skullcap Valerian

α₂δ VDCC blockers	Gabapentin Gabapentin enacarbil Phenibut Pregabalin

Antidepressants	SSRIs SNRIs SARIs TCAs TeCAs MAOIs; Others: Agomelatine Bupropion Vilazodone Vortioxetine

Sympatholytics	Beta blockers (e.g., propranolol) Clonidine Dexmedetomidine Guanfacine Prazosin

Others	Benzoctamine Cannabidiol Cycloserine Fabomotizole Hydroxyzine Kanna Lavender Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane^‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum

v t e Peripheral vasodilators (C04)

Phenylethanolamine derivatives	Isoxsuprine Buphenine Bamethan

Alpha blockers	Non-selective Tolazoline Phentolamine Selective α₁-blockers Alfuzosin Doxazosin Prazosin Silodosin Tamsulosin Terazosin

Niacin and derivatives	Niacin Nicotinyl alcohol Inositol nicotinate Ciclonicate

Purine derivatives	Pentifylline Xantinol nicotinate Pentoxifylline Etofylline nicotinate

Ergot alkaloids	Ergoloid Nicergoline Dihydroergocristine

Other peripheral vasodilators	Cyclandelate Phenoxybenzamine Vincamine Moxisylyte Bencyclane Vinburnine Sulcotidil Buflomedil Naftidrofuryl Butalamine Visnadine Cetiedil Cinepazide Ifenprodil Azapetine Fasudil

匿名

検索

案内

案内

prazosin hydrochloride