TRIMETHAPHAN

Details

Stereochemistry	MIXED
Molecular Formula	C22H25N2OS
Molecular Weight	365.512
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 4
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

O=C1N(CC2=CC=CC=C2)C3C[S+]4CCCC4C3N1CC5=CC=CC=C5

InChI

InChIKey=CHQOEHPMXSHGCL-UHFFFAOYSA-N

InChI=1S/C22H25N2OS/c25-22-23(14-17-8-3-1-4-9-17)19-16-26-13-7-12-20(26)21(19)24(22)15-18-10-5-2-6-11-18/h1-6,8-11,19-21H,7,12-16H2/q+1

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/mmx/trimethaphan-camsylate.html | https://www.ncbi.nlm.nih.gov/pubmed/8618259

Trimethaphan (or Trimethaphan camsylate), a ganglionic blocking agent and an antihypertensive drug, was marketed under the brand name Arfonad. Arfonad is indicated to induce systemic arterial hypotension in patients undergoing major surgery and to treat severe systemic hypertension, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension. Trimethaphan prevents stimulation of postsynaptic receptors by competing with acetylcholine for these receptor sites. Additional effects may include direct peripheral vasodilation and release of histamine. This drug was discontinued because of the competition from newer drugs that are more selective in their actions and effects.

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008983	Primary		Approved 8429	ARFONAD Approved Use Hypotension, controlled (induction and maintenance) - Trimethaphan is indicated for production of controlled hypotension during surgery to reduce bleeding into the surgical field. Hypertension (treatment) - Trimethaphan is indicated for rapid reduction of blood pressure in the treatment of hypertensive emergencies, especially in patients with acute dissecting aneurysm, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension.

Doses

Dose	Population	Adverse events
9 mg/min 1 times / day multiple, intravenous (mean) Studied dose Dose: 9 mg/min, 1 times / day Route: intravenous Route: multiple Dose: 9 mg/min, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/938175/	unhealthy, 23 to 66 years n = 4 Health Status: unhealthy Condition: hypertension Age Group: 23 to 66 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/938175/	Disc. AE: Respiratory arrest... AEs leading to discontinuation/dose reduction: Respiratory arrest Sources: https://pubmed.ncbi.nlm.nih.gov/938175/
0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	Other AEs: Yawning, Sensation of warmth... Other AEs: Yawning Sensation of warmth Nausea Vomiting Pallor Dizziness Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/

AEs

AE	Significance	Dose	Population
Respiratory arrest	Disc. AE	9 mg/min 1 times / day multiple, intravenous (mean) Studied dose Dose: 9 mg/min, 1 times / day Route: intravenous Route: multiple Dose: 9 mg/min, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/938175/	unhealthy, 23 to 66 years n = 4 Health Status: unhealthy Condition: hypertension Age Group: 23 to 66 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/938175/
Dizziness		0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/
Nausea		0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/
Pallor		0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/
Sensation of warmth		0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/
Vomiting		0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/
Yawning		0.115 mg/kg 1 times / day single, intravenous (mean) Studied dose Dose: 0.115 mg/kg, 1 times / day Route: intravenous Route: single Dose: 0.115 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/	pregnant, adult n = 56 Health Status: pregnant Age Group: adult Sex: F Population Size: 56 Sources: https://pubmed.ncbi.nlm.nih.gov/13059864/

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1L2MN5
ABI Chem	AC1Q6LI1
Alfa Chemistry	ACM68917
BOC Sciences	21035-85-8
BOC Sciences	68-91-7
BOC Sciences	7187-66-8
ChemMol	99147727	http://www.chemmol.com/chemmol/99147727.html
Compound Cloud	23576
Compound Cloud	441310
MuseChem	I009884
MuseChem	M019330
THE BioTek	bt-425772	https://www.thebiotek.com/product/others/bt-425772
Tetrahedron	TS74953
Toronto Research Chemicals	T344755
Toronto Research Chemicals	T795435
ZINC	ZINC000003831581	http://zinc15.docking.org/substances/ZINC000003831581
ZINC	ZINC000003938748	http://zinc15.docking.org/substances/ZINC000003938748
ZINC	ZINC000100308855	http://zinc15.docking.org/substances/ZINC000100308855
ZINC	ZINC000100308860	http://zinc15.docking.org/substances/ZINC000100308860
ZINC	ZINC000207869944	http://zinc15.docking.org/substances/ZINC000207869944
eMolecules	110042105
eMolecules	313119497
eNovation Chemicals	D673675	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673675

PubMed

Title	Date	PubMed
[The effects of sodiumnitroprusside and trimethaphan induced hypotension on haemodynamics and myocardial oxygen consumption (author's transl)].	1976 Jan	1259127
Pyramidal tract responses (PTR) during hypoxia and hypotension.	1976 Sep-Oct	960174
Selective osmoreceptor dysfunction in the syndrome of chronic hypernatremia.	1977 Apr	849975
Canine systemic and cerebral effects of hypotension induced by hemorrhage, trimethaphan, halothane, or nitroprusside.	1977 Mar	842872
[Electrocardiographic changes observed during the use of trimethaphan in the treatment of malignant arterial hypertension].	1978 Aug	727981
Postischemic brain oxygenation with barbiturate therapy in rats.	1979 Aug	37043
Cerebral energy levels during trimethaphan-induced hypotension in the rat: effects of light versus deep halothane anesthesia.	1979 Jan	760601
[Use of methoxamine in trimethaphan-induced hypotension].	1979 Jan	424896
Prolonged apnea following trimethaphan and succinylcholine.	1979 Jan	216287
[A comparison of the metabolic effects of hypotension induced by arteriotomy, trimethaphan, nitroprusside, or deep halothane in dog (author's transl)].	1981 Sep	7328742
[The effects of controlled hypotension induced by prostaglandin E1 and trimethaphan on coronary and systemic hemodynamics and myocardial contractility (author's transl)].	1982 Apr	7202062
Cerebral and systemic effects of hypotension induced by trimetaphan or nitroprusside in dogs.	1982 Dec	7158277
Autoregulation of myocardial blood flow under controlled hypotension in the dog.	1982 Jun	7113627
Trimethaphan-induced hypotension: effect on renal function.	1982 Nov	7139398
Altered osmotic threshold for vasopressin release and impaired thirst sensation: additional abnormalities in Kallmann's syndrome.	1982 Oct	7107821
Changes in cardiac output and systemic arterial pressure after insertion of acrylic cement during trimetaphan, sodium nitroprusside and glycerol trinitrate-induced hypotension. A comparison with changes during normotension.	1983 Aug	6411105
Hemodynamics and myocardial metabolism under deliberate hypotension. An experimental study in dogs.	1983 Dec	6673474
[Effect of hypotension induced by trimethaphan and nitroglycerin on intraocular pressure in man].	1983 Feb	6406719
Profound arterial hypotension in dogs: brain electrical activity and organ integrity.	1983 Jan	6848019
Regional blood flows during induced hypotension produced by nitroprusside or trimethaphan in the rhesus monkey.	1985 Aug	4014741
The influence of trimethaphan (Arfonad)-induced hypotension with and without spine distraction on canine spinal cord blood flow.	1986 Apr	3715622
[Effect of trimethaphan-induced hypotension on pituitary-adrenocortical function].	1986 Mar	3012136
[Effect of trimethaphan-induced hypotension on carbohydrate metabolism].	1986 Oct	3543428
The effect of trimethaphan-induced hypotension on canine spinal cord blood flow. Measurement at different cord levels using radiolabelled microspheres.	1988 May	3187693
The hemodynamic and metabolic changes in prostaglandin E1-induced hypotension in dogs--a comparative study with trimetaphan-induced hypotension.	1989 Sep 1	15236040
[Effects of induced hypotensive anesthesia on the blood coagulation-fibrinolysis system measured by thrombelastography--comparison between prostaglandin E1 and trimethaphan].	1992 Jan	1545507
[Pharmacokinetics of epidurally administered bupivacaine during prostaglandin E1- or trimetaphan-induced hypotension].	1992 May	1608154
Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.	1993 Nov	8302922
Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.	1994 Apr	8022855
[Effect of deliberate hypotension on renal functions during epidural block plus inhalation anesthesia: a comparison of prostaglandin E1 and trimethaphan].	1994 Oct	7815696
Cerebral blood flow distribution during induced hypotension with haemorrhage, trimetaphan or nitroprusside in rats.	1995 Jun	7640125
Differential microcirculation dynamics during deliberate hypotension induced by nicardipine, PGE1 and trimethaphan in rat mesentery.	1995 Nov	8590494
Trimetaphan may cause coronary artery spasm.	1995 Sep	8542864
Cerebral blood-flow responses to induced hypotension and to CO2 inhalation in patients with major cerebral artery occlusive disease: a positron-emission tomography study.	1999 Feb	10090598

Patents

Sample Use Guides

In Vivo Use Guide

Controlled hypotension during surgery: Initial: Intravenous infusion, 3 to 4 mg per minute, adjusted according to response. Maintenance: Intravenous infusion, 300 mcg (0.3 mg) to 6 mg per minute. Hypertensive emergency: Initial: Intravenous infusion, 500 mcg (0.5 mg) to 1 mg per minute, adjusted according to response. Maintenance: Intravenous infusion, 1 to 5 mg per minut

Route of Administration: Intravenous

Name

Type

Language

TRIMETHAPHAN

Common Name

English

TRIMETAPHAN

Common Name

English

THIENO(1',2':1,2)THIENO(3,4-D)IMIDAZOLIUM, DECAHYDRO-2-OXO-1,3-BIS(PHENYLMETHYL)-

Systematic Name

English

TRIMETHAPHAN CATION

Common Name

English

TRIMETHAPHAN ION

Common Name

English

Trimetaphan [WHO-DD]

Common Name

English

1,3-DIBENZYL-2-OXODECAHYDROTHIENO(1',2':1,2)THIENO(3,4-D)IMIDAZOL-5-IUM

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QC02BA01