Trimetaphan camsilate

Last updated
Trimetaphan camsilate
Trimetaphan camsilate.svg
Trimetaphan camsilate 3D ball.png
Clinical data
Trade names Arfonad
Routes of
administration
Oral, IM, IV
ATC code
Pharmacokinetic data
Excretion Renal, mostly unchanged
Identifiers
  • 3,5-dibenzyl-4-oxo-8λ4-thia-3,5-diazatricyclo[6.3.0.02,6]undecan-8-ylium (7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate
CAS Number
PubChem CID
DrugBank
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.633 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H25N2OS(free base)
Molar mass 365.52 g·mol−1
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Trimetaphan camsilate (INN) or trimethaphan camsylate (USAN), trade name Arfonad, is a sympatholytic drug used in rare circumstances to lower blood pressure.

Contents

Trimetaphan is a ganglionic blocker: it counteracts cholinergic transmission at a specific type of nicotinic acetylcholine receptors in the autonomic ganglia and therefore blocks both the sympathetic nervous system and the parasympathetic nervous system. It acts as a non-depolarizing competitive antagonist at the nicotinic receptor, is short-acting, and is given intravenously.

It was discovered by Leo Sternbach. [1]

Effects

Trimetaphan is a sulfonium compound and therefore carries a positive charge. Being charged, it cannot cross lipid cell membranes, such as those that comprise the blood–brain barrier. Due to this, trimethaphan does not have any effect on the central nervous system.

The ciliary muscle of the eye functions to round the lens for accommodation and is controlled mainly by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle cannot contract (cycloplegia) and the patient loses the ability to focus their eyes.

Trimetaphan has a strong effect on the cardiovascular system. The size of blood vessels is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the blood vessels causes them to get larger (vasodilation) which has the effect of lowering blood pressure. Postural hypotension is a common side effect of such drugs. Trimethaphan causes a histamine release which further lowers blood pressure. Effects on the heart include a decreased force of contraction and an increase in heart rate (tachycardia). Reflexive tachycardia can be diminished or undetected because trimetaphan is also blocking the sympathetic ganglia innervating the heart.

The motility of the gastrointestinal tract is regulated by the parasympathetic system, and blockage of this input results in diminished motility and constipation.

A rare side effect of trimethaphan administration is sudden respiratory arrest. The mechanism behind it is unknown, as trimethaphan does not appear to block neuromuscular transmission, and respiratory arrest is not an expected consequence of ganglionic blockage. [2]

Therapeutic uses

The therapeutic uses of trimetaphan are very limited due to the competition from newer drugs that are more selective in their actions and effects produced. It is occasionally used to treat a hypertensive crisis and dissecting aortic aneurysm, to treat pulmonary edema, and to reduce bleeding during neurosurgery.

Related Research Articles

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A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system, this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system, there are both sympathetic and parasympathetic ganglia which contain the cell bodies of postganglionic sympathetic and parasympathetic neurons respectively.

<span class="mw-page-title-main">Acetylcholine</span> Organic chemical and neurotransmitter

Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.

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A ganglionic blocker is a type of medication that inhibits transmission between preganglionic and postganglionic neurons in the autonomic nervous system, often by acting as a nicotinic receptor antagonist. Nicotinic acetylcholine receptors are found on skeletal muscle, but also within the route of transmission for the parasympathetic and sympathetic nervous system. More specifically, nicotinic receptors are found within the ganglia of the autonomic nervous system, allowing outgoing signals to be transmitted from the presynaptic to the postsynaptic cells. Thus, for example, blocking nicotinic acetylcholine receptors blocks both sympathetic (excitatory) and parasympathetic (calming) stimulation of the heart. The nicotinic antagonist hexamethonium, for example, does this by blocking the transmission of outgoing signals across the autonomic ganglia at the postsynaptic nicotinic acetylcholine receptor.

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References

  1. Bause GS (1 August 2017). "From Coenzyme R to "Arfonad" and from Vitamin H to Hypotension". Anesthesiology. 127 (2): 381–381. doi:10.1097/ALN.0000000000001771. ISSN   0003-3022.
  2. Dale RC, Schroeder ET (July 1976). "Respiratory paralysis during treatment of hypertension with trimethaphan camsylate". Archives of Internal Medicine. 136 (7): 816–8. doi:10.1001/archinte.1976.03630070060018. PMID   938175.

Further reading