Trimetaphan camsilate

Trimetaphan camsilate

Clinical data
Trade names	Arfonad
Routes of administration	Oral, IM, IV
ATC code	C02BA01 ( WHO )
Pharmacokinetic data
Excretion	Renal, mostly unchanged
Identifiers
IUPAC name 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	68-91-7  Y
PubChem CID	23576
DrugBank	DB01116  N
UNII	8W556014K9
KEGG	D00612
ChEMBL	ChEMBL1245  N
CompTox Dashboard (EPA)	DTXSID3023710
ECHA InfoCard	100.000.633
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), sold under the trade name Arfonad, is a sympatholytic drug that is infrequently used to lower blood pressure.

Trimetaphan is a ganglionic blocker: it counteracts cholinergic transmission at the 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 functions as a non-depolarizing competitive antagonist at the nicotinic receptor, has a short duration of action, and is administered intravenously.

It was discovered by Leo Sternbach. ^[1]

Effects

Trimetaphan is a sulfonium compound and, as such, carries a positive charge. This charge prevents it from crossing lipid cell membranes, including those that comprise the blood–brain barrier. Consequently, trimethaphan has no effect on the central nervous system.

The ciliary muscle of the eye functions to round the lens for accommodation and is primarily controlled by parasympathetic system input. When a ganglion-blocking drug is administered, the ciliary muscle is unable to contract (cycloplegia), and the patient loses the ability to focus.

Trimetaphan has a significant effect on the cardiovascular system. Blood vessel size is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the blood vessels causes them to dilate (vasodilation), which lowers blood pressure. Postural hypotension is a common side effect of these drugs. Trimethaphan causes histamine release, further decreasing 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 also blocks 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 this is unknown, as trimethaphan does not appear to block the neuromuscular transmission, and respiratory arrest is not an expected consequence of ganglionic blockage. ^[2]

Therapeutic uses

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

References

1. Bause GS (1 August 2017). "From Coenzyme R to "Arfonad" and from Vitamin H to Hypotension". Anesthesiology. 127 (2): 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

• Anderson SM (July 1955). "Controlled hypotension with arfonad in paediatric surgery". British Medical Journal. 2 (4931): 103–4. doi:10.1136/bmj.2.4931.103. PMC   1980290 . PMID   14378656.
• Kling TF, Wilton N, Hensinger RN, Knight PR (April 1986). "The influence of trimethaphan (Arfonad)-induced hypotension with and without spine distraction on canine spinal cord blood flow". Spine. 11 (3): 219–24. doi:10.1097/00007632-198604000-00007. PMID   3715622. S2CID   24029902.
• Moyer JH, Handley CA (April 1955). "Renal and cardiovascular hemodynamic response to ganglionic blockade with pendiomide and a comparison with hexamethonium and arfonad" . The Journal of Pharmacology and Experimental Therapeutics. 113 (4): 383–92. doi:10.1016/S0022-3565(25)11524-3. PMID   14368507.
• Ulm AH (February 1959). "The treatment of primary priapism with arfonad". The Journal of Urology. 81 (2): 291–3. doi:10.1016/S0022-5347(17)66009-9. PMID   13631819.
• Petrides G, Maneksha F, Zervas I, Carasiti I, Francis A (March 1996). "Trimethaphan (Arfonad) control of hypertension and tachycardia during electroconvulsive therapy: a double-blind study". Journal of Clinical Anesthesia. 8 (2): 104–9. doi:10.1016/0952-8180(95)00192-1. PMID   8695090.
• Tewfik GI, Wells BG (July 1957). "The use of arfonad for the alleviation of cardio-vascular stress following electro-convulsive therapy". The Journal of Mental Science. 103 (432): 636–44. doi:10.1192/bjp.103.432.636. PMID   13449573.
• Rowe GG, Afonso S, Lugo JE, Boake WC (1964). "Systemic and Coronary Hemodynamic Effects of Trimethaphan Camphorsulfonate (Arfonad) in the Dog". Anesthesiology. 25 (2): 156–60. doi: 10.1097/00000542-196403000-00008 . PMID   14156542. S2CID   36791833.