Tetramethylammonium

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Tetramethylammonium (TMA) is the simplest quaternary ammonium cation. Its formula is [N(CH3)4]+ (often written as C4H12N+). Four methyl groups are attached to a central nitrogen, giving a positively charged ion that forms salts with various counter-ions such as chloride or hydroxide. It is isoelectronic with neopentane and is highly hydrophilic.

TMA salts are used in chemical synthesis and in pharmacological research. It does not color its salts. In toxicology literature, the name “tetramine” is sometimes used, but it is non-systematic and can refer to other substances as well. The acronym “TMA” can also stand for other compounds in pharmacology.

TMA occurs naturally in some marine organisms (certain Neptunea whelks) and has been found in one plant, Courbonia virgata, as well as in the rare mineral Tsaregorodtsevite. It is typically prepared by reacting trimethylamine with methyl chloride to form the chloride salt, and other salts can be made by salt metathesis (for example, tetramethylammonium borohydride from the hydroxide salt).

Properties: The TMA cation is hydrophilic, with a tetrahedral arrangement around nitrogen. The ionic radius is about 0.322 nm, and the effective diameter is roughly 0.6 nm. The octanol–water partition coefficient for the iodide salt is very low (log P ≈ −3.92), indicating strong preference for water.

Pharmacology: TMA is a cholinergic agent that mimics many actions of acetylcholine. It can stimulate nicotinic and muscarinic receptors, initially depolarizing nerves and muscles and then blocking neurotransmission in autonomic ganglia. In skeletal muscle, it may cause fasciculations followed by paralysis due to depolarization. Researchers often use TMA salts (chloride, bromide, iodide) to study its effects without interference from the counter-ion.

Pharmacokinetics: TMA salts are well absorbed from the gut. In animals, distribution is rapid with high levels in kidney and liver. Metabolism is minimal, and most of the dose is excreted in urine unchanged.

Toxicology: In humans, ingestion can cause nausea, vomiting, headache, dizziness, blurred vision, photophobia, loss of balance, and skin reactions; symptoms typically begin within about 30 minutes and usually resolve within a few hours. The estimated lethal oral dose is around 3–4 mg/kg. Animal data vary by species and salt form, but provide analogous toxicity estimates.