Page last updated: 2024-12-06

trimethaphan

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Trimethaphan is a ganglionic blocker that acts by competitively antagonizing acetylcholine at nicotinic receptors in autonomic ganglia. It is synthesized by reacting 3-(2,6-dimethylpiperidino)propan-1-ol with 1-bromo-2-chloroethane. Trimethaphan has a rapid onset of action and a short duration of action, making it suitable for use in the management of hypertensive emergencies. Trimethaphan is studied for its potential use in the treatment of various conditions, including hypertensive crises, pheochromocytoma, and acute aortic dissection. It is also being investigated for its potential use in the prevention of intracerebral hemorrhage.'

Trimethaphan: A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

trimethaphan : A complex heterocyclic sulfonium compound with an imidazolium core, used to treat hypertension. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID23576
CHEMBL ID1201329
CHEBI ID9728
MeSH IDM0021990

Synonyms (30)

Synonym
PDSP1_000122
trimethaphan
7187-66-8
C07174
DB01116
trimetaphanum
thimethaphan
trimetaphan
PDSP2_000122
1,3-dibenzyl-2-oxodecahydrothieno[1',2':1,2]thieno[3,4-d]imidazol-5-ium
CHEBI:9728 ,
thieno(1',2':1,2)thieno(3,4-d)imidazol-5-ium, decahydro-2-oxo-1,3-bis(phenylmethyl)-
trimethaphan ion
trimethaphan cation
CHEMBL1201329
bdbm82545
cas_441310
nsc_441310
unii-6g8x656t45
6g8x656t45 ,
thieno(1',2':1,2)thieno(3,4-d)imidazol-5-ium, decahydro-2-oxo-1,3-bis(phenylmethyl)- (van)
hsdb 7676
1,3-dibenzyl-2-oxodecahydrothieno(1',2':1,2)thieno(3,4-d)imidazol-5-ium
trimetaphan [who-dd]
7728-39-4
thieno(1',2':1,2)thieno(3,4-d)imidazolium, decahydro-2-oxo-1,3-bis(phenylmethyl)-
DTXSID8043787
3,5-dibenzyl-4-oxo-8$l^{4}-thia-3,5-diazatricyclo[6.3.0.0^{2,6}]undecan-8-ylium
3,5-dibenzyl-8-thionia-3,5-diazatricyclo[6.3.0.02,6]undecan-4-one
Q9361596

Research Excerpts

Overview

Trimethaphan camsylate is a potent antihypertensive drug used to induce systemic arterial hypotension in patients undergoing major surgery and to treat severe systemic hypertension. It was found to be a potent noncompetitive inhibitor of pseudocholinesterase.

ExcerptReferenceRelevance
"Trimethaphan camsylate is a potent antihypertensive drug used to induce systemic arterial hypotension in patients undergoing major surgery and to treat severe systemic hypertension. "( Ultra-high dose trimethaphan in an infant with severe hypertension.
Hammer, GB, 1996
)
2.08
"Trimethaphan was found to be a potent noncompetitive inhibitor of pseudocholinesterase (KI = 0.24 micronM)."( Effects of trimethaphan and sodium nitroprusside on hydrolysis of succinylcholine in vitro.
Lanks, KW; Sklar, GS, 1977
)
1.37

Actions

ExcerptReferenceRelevance
"Trimethaphan does not increase CSF pressure."( Trimethaphan versus sodium nitroprusside for the control of proximal hypertension during thoracic aortic cross-clamping: the effects on spinal cord ischemia.
Bermudez, R; D'Ambra, T; Eide, TR; Lebowitz, P; Levine, D; Newman, SB; Schiff, GA; Simpson, JI, 1996
)
2.46

Treatment

ExcerptReferenceRelevance
"Treatment with trimethaphan (10(-4)-10(-3)M) protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine."( Trimethaphan is a direct arterial vasodilator and an alpha-adrenoceptor antagonist.
Harioka, T; Hatano, Y; Mori, K; Toda, N, 1984
)
2.05

Pharmacokinetics

ExcerptReferenceRelevance
"The effects of prostaglandin E1 (PGE1) and trimetaphan (TMP) on the plasma concentrations and derived pharmacokinetic parameters of bupivacaine were studied in 14 women after its epidural administration."( [Pharmacokinetics of epidurally administered bupivacaine during prostaglandin E1- or trimetaphan-induced hypotension].
Hamakawa, T; Sakimura, S; Takasaki, M; Takeshita, M, 1992
)
0.28

Compound-Compound Interactions

ExcerptReferenceRelevance
"The effect of trimetaphan alone and in combination with pancuronium, tubocurarine or metocurine (dimethyl tubocurarine) has been examined on the rat phrenic nerve diaphragm preparation."( The neuromuscular blocking effect of trimetaphan alone and in combination with different non-depolarizing muscle relaxants in the rat.
Pollard, BJ; van der Spek, AF, 1987
)
0.27

Dosage Studied

Trimethaphan (10(-4)-10(-3)M) shifted the dose-response curve for norepinephrine in mesenteric arteries to the right. It failed to influence the contractile response to 25 mM KCl.

ExcerptRelevanceReference
" Nitroprusside (15 patients) was associated with a small increase in mean lactate, but at low dosage there was a small decrease."( Metabolic effects of induced hypotension with trimetaphan and sodium nitroprusside.
Drummond, GB; MacRae, WR; Wildsmith, JA, 1979
)
0.26
" There was a strict dose-response relationship between duration of ischemia and mortality."( Forebrain ischemia in the rat. Relation between duration of ischemia, use of adjunctive ganglionic blockade and long-term recovery.
Arfors, KE; Gerdin, B; Grøgaard, B,
)
0.13
" Cumulative dose-response curves were constructed for 8-OH-DPAT, ipsapirone and clonidine."( Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats.
Fozard, JR; Ramage, AG, 1987
)
0.27
" The dose-response curves for inhibition of glutamate responses by trimethaphan suggest that trimethaphan is not a competitive glutamate antagonist."( Trimethaphan as a glutamate inhibitor at the crayfish neuromuscular junction.
Ishida, M; Shinozaki, H, 1983
)
1.94
" Trimethaphan (10(-4)-10(-3)M) shifted the dose-response curve for norepinephrine in mesenteric arteries to the right, but failed to influence the contractile response to 25 mM KCl."( Trimethaphan is a direct arterial vasodilator and an alpha-adrenoceptor antagonist.
Harioka, T; Hatano, Y; Mori, K; Toda, N, 1984
)
2.62
" A readily controllable hypotension was produced with considerable reduction in the dosage of these drugs compared to their used individually."( Induced hypotension with a mixture of sodium nitroprusside and trimetaphan camsylate.
Dale, BA; MacRae, WR; Wildsmith, JA, 1981
)
0.26
" The whole-cell dose-response curve suggests that activation of current by ACh increases up to at least 100 microM and that multiple ligand binding steps are involved."( Activation of nicotinic acetylcholine receptors on cultured Drosophila and other insect neurones.
Albert, JL; Lingle, CJ, 1993
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
vasodilator agentA drug used to cause dilation of the blood vessels.
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
anaesthesia adjuvantAny substance that possesses little anaesthetic effect by itself, but which enhances or potentiates the anaesthetic action of other drugs when given at the same time.
nicotinic antagonistAn antagonist at the nicotinic cholinergic receptor.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
sulfonium compound
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Research

Studies (845)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990663 (78.46)18.7374
1990's121 (14.32)18.2507
2000's52 (6.15)29.6817
2010's9 (1.07)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 45.07

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index45.07 (24.57)
Research Supply Index6.90 (2.92)
Research Growth Index3.90 (4.65)
Search Engine Demand Index76.15 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (45.07)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials61 (6.54%)5.53%
Reviews42 (4.50%)6.00%
Case Studies32 (3.43%)4.05%
Observational0 (0.00%)0.25%
Other798 (85.53%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (10)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Reduction in Splanchnic Capacitance Contributes to Sympathetically Dependent Hypertension in Autonomic Aim 1 of Rare Diseases Clinical Research Network (RDCRN) Project 2 [NCT02726711]Phase 12 participants (Actual)Interventional2016-04-30Active, not recruiting
Cardiovascular Effects of Angiotensin (1-7) in Essential Hypertension [NCT02245230]Phase 134 participants (Anticipated)Interventional2015-01-31Active, not recruiting
The Autonomic Nervous System, Nitric Oxide and TPA Interactions [NCT01137253]Phase 121 participants (Actual)Interventional2010-06-30Completed
Obesity, Hypertension in African American Women, Neuro-metabolic Mechanism [NCT01122407]Phase 134 participants (Actual)Interventional2010-01-31Completed
Role of Sympathetic Activity and Splanchnic Capacitance in Hypertension [NCT02425566]Phase 112 participants (Anticipated)Interventional2015-04-30Active, not recruiting
Autonomic Nervous System and Chronic Fatigue Syndrome [NCT00580619]Phase 1170 participants (Actual)Interventional2007-04-30Completed
The Autonomic Nervous System and Obesity [NCT00179023]Phase 1128 participants (Actual)Interventional2003-04-30Completed
The Autonomic Nervous System and the Metabolic Syndrome [NCT00580957]56 participants (Actual)Interventional2008-08-31Completed
Cardiovascular Regulation: Autonomic/Metabolic Mechanisms PO1 HL56693, Project 4: Cardiovascular Regulation: Autonomic/Metabolic Mechanisms [NCT00178919]112 participants (Actual)Interventional2002-08-31Completed
Acute Sympathetic Blockade and Endogenous Glucose Production [NCT03028571]Phase 10 participants (Actual)Interventional2017-04-17Withdrawn(stopped due to The investigators decided not to perform the study. No participants have been enrolled.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00178919 (2) [back to overview]Change in Systolic Blood Pressure
NCT00178919 (2) [back to overview]Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition
NCT00580957 (1) [back to overview]Insulin Resistance

Change in Systolic Blood Pressure

L-NMMA (nitric oxide synthase inhibitor) was infused intravenously at different doses for 15 minutes each, after blocking the autonomic nervous system with trimethaphan. The change in systolic blood pressure at the end of the highest tolerated dose is the main outcome. Trimethaphan infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex. (NCT00178919)
Timeframe: At the end of the highest tolerated dose of IV infusion of L-NMMA

Interventionmm Hg (Mean)
Autonomic Failure Patients43
Hypertensives and Controls21

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Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition

Systolic blood pressure at the highest tolerated dose of IV infusion of L-NMMA during autonomic nervous system blockade with trimethaphan. Trimethaphan, infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex. (NCT00178919)
Timeframe: End of 15 minutes of infusion of L-NMMA at the highest tolerated dose

Interventionmm Hg (Mean)
Autonomic Failure Patients152
Hypertensives and Controls136

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Insulin Resistance

Glucose infusion rate in mg/kg/min (NCT00580957)
Timeframe: Last 30 minutes of a two hour insulin clamp

Interventionmg/kg/min (Mean)
Blocked3.8
Intact3.1

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