Guanethidine: Difference between revisions

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Guanethidine
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a600027
ATC code	C02CC02 (WHO) S01EX01 (WHO);
Pharmacokinetic data
Elimination half-life	1.5 days
Identifiers
	IUPAC name 2-[2-(azocan-1-yl)ethyl]guanidine;
CAS Number	645-43-2 ;
PubChem CID	3518;
DrugBank	DB01170 ;
ChemSpider	3398 ;
UNII	5UBY8Y002G;
KEGG	D08030 ;
ChEBI	CHEBI:5557 ;
ChEMBL	ChEMBL765 ;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C10H22N4
Molar mass	198.309 g/mol
3D model (JSmol)	Interactive image;
	SMILES N(=C(\N)N)\CCN1CCCCCCC1;
	InChI InChI=1S/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13) ; Key:ACGDKVXYNVEAGU-UHFFFAOYSA-N ;
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VisualWikitext

Latest revision as of 12:45, 8 April 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself (NET, uptake 1), and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine.It may also inhibit the release of granules by decreasing norepinephrine.

Side effects

Side effects include orthostatic and exercise hypotension, sexual dysfunction (delayed or retrograde ejaculation), and diarrhea.

Pharmacology

Guanethidine is transported by uptake 1 into the presynaptic terminal transported by Norepinephrine transporter (NET). (In this it competes with norepinephrine so can potentiate exogenously applied norepinephrine.) It becomes concentrated in norepinephrine transmitter vesicles, replacing norepinephrine in these vesicles. This leads to a gradual depletion of norepinephrine stores in the nerve endings. Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential. Spontaneous release is not affected.

Uses

Guanethidine was once a mainstay for hypertension resistant to other agents, and was often used safely during pregnancy, but it is no longer used in the US due to lack of availability. It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a hypertensive emergency.

Intravenous nerve block (Bier block) using guanethidine has been used to treat chronic pain caused by complex regional pain syndrome.^[1]

Chemical synthesis

Guanethidine is synthesized beginning with the alkylation of azocine with chloroacetonitrile. This reaction which forms 1-azocinylacetonitrile, which can be reduced into 1-(2-aminoethyl)azocine by using lithium aluminium hydride as a reductant. This compound reacts with S-methylthiourea forming guanethidine.^[2]^[3]^[4]

References

↑ Joyce PI, Rizzi D, Caló G, Rowbotham DJ, Lambert DG (November 2002). "The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens". Anesth. Analg. 95 (5): 1339–43, table of contents. doi:10.1097/00000539-200211000-00045. PMID 12401623.
↑ R.P. Mull, Template:US Patent (1960)
↑ R.P. Mull, Template:US Patent (1961)
↑ R.P. Mull, Template:US Patent (1962)

Template:Antiglaucoma preparations and miotics

Template:Antihypertensive-stub

[pmid12401623-1] Joyce PI, Rizzi D, Caló G, Rowbotham DJ, Lambert DG (November 2002). "The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens". Anesth. Analg. 95 (5): 1339–43, table of contents. doi:10.1097/00000539-200211000-00045. PMID 12401623.

[2] R.P. Mull, Template:US Patent (1960)

[3] R.P. Mull, Template:US Patent (1961)

[4] R.P. Mull, Template:US Patent (1962)

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-{{drugbox
+{{Drugbox
-| IUPAC_name = 2-(2-azocan-1-ylethyl)guanidine
+| Verifiedfields = changed
-| image = Guanethidine_svg.png
+| verifiedrevid = 461124124
+| IUPAC_name = 2-[2-(azocan-1-yl)ethyl]guanidine
+| image = Guanethidine Wiki Str.png
+| alt = Skeletal formula of guanethidine
+| width = 250
+| image2 = Guanethidine BnS.png
+| alt2 = Ball-and-stick model of the guanethidine molecule
+<!--Clinical data-->
+| tradename =
+| Drugs.com = {{drugs.com|CONS|guanethidine}}
+| MedlinePlus = a600027
+| pregnancy_category =
+| legal_status =
+| routes_of_administration =
+<!--Pharmacokinetic data-->
+| bioavailability =
+| protein_bound =
+| metabolism =
+| elimination_half-life = 1.5 days
+<!--Identifiers-->
+| CASNo_Ref = {{cascite|correct|CAS}}
+| CAS_number_Ref = {{cascite|correct|??}}
 | CAS_number = 645-43-2
 | ATC_prefix = C02
 | ATC_suffix = CC02
-| ATC_supplemental = {{ATC|S01|EX01}}
+| ATC_supplemental =  {{ATC|S01|EX01}}
 | PubChem = 3518
-| DrugBank = APRD01007
+| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
-| C=10 | H=22 | N=4
+ | DrugBank = DB01170
+| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
+| ChemSpiderID = 3398
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = 5UBY8Y002G
+| KEGG_Ref = {{keggcite|changed|kegg}}
+| KEGG = D08030
+| ChEBI_Ref = {{ebicite|correct|EBI}}
+| ChEBI = 5557
+| ChEMBL_Ref = {{ebicite|correct|EBI}}
+| ChEMBL = 765
+<!--Chemical data-->
+| C=10 | H=22 | N=4
 | molecular_weight = 198.309 g/mol
-| bioavailability =
+| smiles = N(=C(\N)N)\CCN1CCCCCCC1
-| protein_bound =
+| InChI = 1/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13)
-| metabolism =
+| InChIKey = ACGDKVXYNVEAGU-UHFFFAOYAQ
-| elimination_half-life = 1.5 days
+| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
-| pregnancy_category =
+| StdInChI = 1S/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13)
-| legal_status =
+| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
-| routes_of_administration =
+| StdInChIKey = ACGDKVXYNVEAGU-UHFFFAOYSA-N
 }}
 __NOTOC__
-'''For patient information, click [[Guanethidine (patient information)|here]]'''.
 {{SI}}
 {{CMG}}
+==Overview==
+'''Guanethidine''' is an [[antihypertensive]] drug that reduces the release of [[catecholamines]], such as [[norepinephrine]]. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself (NET, uptake 1), and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine.It may also inhibit the release of granules by decreasing norepinephrine.
+==Side effects==
+Side effects include orthostatic and exercise [[hypotension]], [[sexual dysfunction]] (delayed or [[retrograde ejaculation]]), and [[diarrhea]].
+==Pharmacology==
+Guanethidine is transported by uptake 1 into the [[presynaptic terminal]] transported by Norepinephrine transporter (NET). (In this it competes with norepinephrine so can potentiate exogenously applied norepinephrine.) It becomes concentrated in norepinephrine transmitter vesicles, replacing norepinephrine in these vesicles. This leads to a gradual depletion of norepinephrine stores in the nerve endings.
+Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential. Spontaneous release is not affected.
+==Uses==
+Guanethidine was once a mainstay for hypertension resistant to other agents, and was often used safely during pregnancy, but it is no longer used in the US due to lack of availability. It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a [[hypertensive emergency]].
-==Overview==
+Intravenous nerve block ([[Intravenous regional anesthesia|Bier block]]) using guanethidine has been used to treat [[chronic pain]] caused by [[complex regional pain syndrome]].<ref name="pmid12401623">{{cite journal |author=Joyce PI, Rizzi D, Caló G, Rowbotham DJ, Lambert DG |title=The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens |journal=Anesth. Analg. |volume=95 |issue=5 |pages=1339–43, table of contents |date=November 2002 |pmid=12401623 |doi= 10.1097/00000539-200211000-00045|url=http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=12401623}}</ref>
-'''Guanethidine''' is an [[antihypertensive]] drug that reduces the release of [[catecholamines]], such as noradrenaline. Its mechanism is inhibition of the [[Mg++ATPase dependent pump]]. Side effects include orthostatic and exercise hypotension, sexual dysfunction, and diarrhea.
+==Chemical synthesis==
+Guanethidine is [[organic synthesis|synthesized]] beginning with the alkylation of [[azocine]] with [[chloroacetonitrile]].  This reaction which forms 1-azocinylacetonitrile, which can be reduced into 1-(2-aminoethyl)azocine by using [[lithium aluminium hydride]] as a [[reductant]].  This compound reacts with ''S''-methylthiourea forming guanethidine.<ref>R.P. Mull, {{US Patent|2928829}} (1960)</ref><ref>R.P. Mull, {{US Patent|3006913}} (1961)</ref><ref>R.P. Mull, {{US Patent|3055882}} (1962)</ref>
+:[[File:Guanethidine Syn.png|none|800px]]
-It is no longer available in the US due to side effects and because substantially better drugs are available. It is still licensed in some countries, e.g. UK, for the rapid control of blood pressure in a [[hypertensive emergency]].
+==References==
+{{reflist|2}}
+{{Adrenergics}}
 {{Antihypertensives and diuretics}}
 {{Antiglaucoma preparations and miotics}}
-[[Category:Cardiovascular Drugs]]
+[[Category:Drug]]
-[[Category:Drugs]]
+[[Category:Alpha-adrenergic agonists]]
+[[Category:Guanidines]]
+[[Category:Azocanes]]
+{{antihypertensive-stub}}

v t e Adrenergic receptor modulators
α₁	Agonists: 6-FNE Amidephrine Anisodine Buspirone Cirazoline Corbadrine Desglymidodrine Dexisometheptene Dipivefrine Dopamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etilefrine Etilevodopa Ethylnorepinephrine Indanidine Isometheptene L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Melevodopa Metaraminol Methoxamine Methyldopa Midodrine Naphazoline Norepinephrine Octopamine (drug) Oxymetazoline Phenylephrine Phenylpropanolamine Pseudoephedrine Synephrine Tetryzoline Tiamenidine XP21279 Xylometazoline Antagonists: Abanoquil Adimolol Ajmalicine Alfuzosin Amosulalol Anisodamine Arotinolol Atiprosin Atypical antipsychotics (e.g., brexpiprazole, clozapine, olanzapine, quetiapine, risperidone) Benoxathian Buflomedil Bunazosin Carvedilol Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., ergotamine, dihydroergotamine, lisuride, terguride) Etoperidone Eugenodilol Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 Labetalol mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Niaprazine Nicergoline Niguldipine Pardoprunox Pelanserin Perlapine Phendioxan Phenoxybenzamine Phentolamine Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione) Piperoxan Prazosin Quinazosin Quinidine Ritanserin Silodosin Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, imipramine, trimipramine) Trimazosin Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Urapidil WB-4101 Zolertine
α₂	Agonists: (R)-3-Nitrobiphenyline 4-NEMD 6-FNE Amitraz Apraclonidine Brimonidine Cannabivarin Clonidine Corbadrine Detomidine Dexmedetomidine Dihydroergotamine Dipivefrine Dopamine Droxidopa (L-DOPS) Etilevodopa Ephedrine Ergotamine Epinephrine Etilefrine Ethylnorepinephrine Guanabenz Guanfacine Guanoxabenz L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Lofexidine Medetomidine Melevodopa Methyldopa Mivazerol Naphazoline Norepinephrine Oxymetazoline Phenylpropanolamine Piperoxan Pseudoephedrine Rezatomidine Rilmenidine Romifidine Talipexole Tasipimidine Tetrahydrozoline Tiamenidine Tizanidine Tolonidine Urapidil Vatinoxan XP21279 Xylazine Xylometazoline Antagonists: 1-PP Adimolol Amesergide Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine, brexpiprazole, clozapine, lurasidone, paliperidone, quetiapine, risperidone, zotepine) Azapirones (e.g., buspirone, gepirone, ipsapirone, tandospirone) BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan mCPP Mianserin Mirtazapine NAN-190 Olanzapine Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine SB-269970 Setiptiline Spiroxatrine Sunepitron Tolazoline Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Yohimbine
β	Agonists: Abediterol Alifedrine Amibegron Arbutamine Arformoterol Arotinolol BAAM Bambuterol Befunolol Bitolterol Broxaterol Buphenine Carbuterol Carmoterol Cimaterol Clenbuterol Colterol Corbadrine Denopamine Dipivefrine Dobutamine Dopamine Dopexamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etafedrine Etilefrine Etilevodopa Ethylnorepinephrine Fenoterol Formoterol Hexoprenaline Higenamine Indacaterol Isoetarine Isoprenaline Isoxsuprine L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Levosalbutamol Mabuterol Melevodopa Methoxyphenamine Methyldopa Mirabegron Norepinephrine Orciprenaline Oxyfedrine PF-610355 Phenylpropanolamine Pirbuterol Prenalterol Ractopamine Procaterol Pseudoephedrine Reproterol Rimiterol Ritodrine Salbutamol Salmeterol Solabegron Terbutaline Tretoquinol Tulobuterol Vilanterol Xamoterol XP21279 Zilpaterol Zinterol Antagonists: Acebutolol Adaprolol Adimolol Afurolol Alprenolol Alprenoxime Amosulalol Ancarolol Arnolol Arotinolol Atenolol Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Bornaprolol Brefonalol Bucindolol Bucumolol Bufetolol Bufuralol Bunitrolol Bunolol Bupranolol Butaxamine Butidrine Butofilolol Capsinolol Carazolol Carpindolol Carteolol Carvedilol Celiprolol Cetamolol Cicloprolol Cinamolol Cloranolol Cyanopindolol Dalbraminol Dexpropranolol Diacetolol Dichloroisoprenaline Dihydroalprenolol Dilevalol Diprafenone Draquinolol Ecastolol Epanolol Ericolol Ersentilide Esatenolol Esprolol Eugenodilol Exaprolol Falintolol Flestolol Flusoxolol Hydroxycarteolol Hydroxytertatolol ICI-118,551 Idropranolol Indenolol Indopanolol Iodocyanopindolol Iprocrolol Isoxaprolol Isamoltane Labetalol Landiolol Levobetaxolol Levobunolol Levomoprolol Medroxalol Mepindolol Metipranolol Metoprolol Moprolol Nadolol Nadoxolol Nebivolol Nifenalol Nipradilol Oxprenolol Pacrinolol Pafenolol Pamatolol Pargolol Penbutolol Pindolol Practolol Primidolol Procinolol Pronethalol Propafenone Propranolol Ridazolol Ronactolol Soquinolol Sotalol Spirendolol SR 59230A Sulfinalol Talinolol Tazolol Tertatolol Tienoxolol Tilisolol Timolol Tiprenolol Tolamolol Toliprolol Xibenolol Xipranolol

v t e Antihypertensives (C02) and diuretics (C03)
Sympatholytic agents	Template:Navbox subgroup
Vasodilators	Diazoxide • hydrazinophthalazine (Hydralazine, Dihydralazine, Endralazine, Cadralazine) • Minoxidil • Nitroprusside • Phentolamine
Other antihypertensives	serotonin antagonist (Ketanserin) • endothelin receptor antagonist (Bosentan, Ambrisentan, Sitaxsentan) • MAOI (Pargyline) • THI (Metirosine)
Diuretics	Template:Navbox subgroup