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Methoctramine

Methoctramine
Methoctramine.svg
Methoctramine.jpg
Legal status
Legal status
  • US: Only for research
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
Chemical and physical data
Formula C36H62N4O2
Molar mass 582.90 g/mol
3D model (Jmol)
Solubility in water 20 g/l mg/mL (20 °C)

Methoctramine is a polymethylene tetraamine that acts as a muscarinic antagonist. It preferently binds to the pre-synaptic receptor M2, a muscarinic acetylcholine ganglionic protein complex present basically in heart cells. In normal conditions -absence of methoctramine-, the activation of M2 receptors diminishes the speed of conduction of the sinoatrial and atrioventricular nodes thus reducing the heart rate. Thanks to its apparently high cardioselectivity, it has been studied as a potential parasymphatolitic drug, particularly against bradycardia. However, currently it’s only addressed for research purposes, since the administration to humans is still unavailable.

Methoctramine has been shown to competitively antagonize muscarinic receptors, thus preventing them from binding to the neurotransmitter acetylcholine (and other agonists, such as bethanechol or berberine). At higher concentrations, allosteric properties of methoctramine have also been described.

Biochemical literature distinguishes 5 different types of muscarinic receptors, each of one having a different affinity to methoctramine:

Please note that, the lower the affinity constants are, the more affinity exists.

As shown in the chart above, methoctramine binds preferently to M2 receptors, found mostly in the parasympathetic nerves and atria. There, the activity it develops is clearly related to the contraction process. In presence of acetylcholine, M2 receptors are believed to play an autoinhibitory role in the atria, triggering processes that prevent contraction from occurring. Hence, the presence of the antagonist methoctramine provokes an increase of the heart rate.

In marked contrast of the above, methoctramine has the opposite function in other organs: it inhibits contraction. This occurs especially in the bladder, where, unlike the heart, autoinhibitory processes of this type do not exist.

Recent research, however, led to find the mentioned specialty dubious, rising the possibility of it binding to other types of receptors, such as nicotinic ACh receptors –at micromolar concentrations- or adenosine A3.

The exact effects of methoctramine still remain unknown. However, the few experiments conducted have led to relate this molecule to the following:


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