55-97-0

Hexamethonium is a peripherally-acting nondepolarizing neuromuscular blocking agent that acts as an antagonist of nicotinic acetylcholine receptors (nAChRs). It decreases acetylcholine release induced by carbamoylcholine (Item No. 14486) in isolated cat superior cervical ganglion when used at concentrations of 27.4 and 54.8 μg/ml. It also decreases mean arterial pressure in unanesthetized rats when administered at a dose of 40 mg/kg. Intraventricular administration of hexamethonium (18 ng, i.c.v.) induces signs of nicotine abstinence, including shaking, writhing, and chewing in nicotine-dependent rats. Formulations containing hexamethonium were previously used in the treatment of hypertension.

White crystalline powder and agglomerates

Bistrium,Squibb,US,1951

Hexamethylene diamine (116 g), sodium carbonate (466 g), and water (800 ml) were heated to 60°C, and dimethyl sulfate (830 g) added with stirring over 1% hours keeping the temperature below 90°C. The reaction mixture was then stirred at 90°C for 2 hours, then cooled to 20°C, acetone (1,200 ml) added and the whole cooled to 0°C.
The solid formed was removed by filtration and washed with acetone (150 ml). Filtrate and washings were diluted with water to 4 liters and heated to 60°C under reflux. To this was added a solution prepared from embonic acid (388 g), sodium hydroxide (80 g) and water (5 liters), the whole refluxed for 10 minutes and thereafter allowed to cool overnight.
The resultant embonate (530 g) was filtered off, washed twice with a solution of acetone (75 ml) in water (425 ml), and dried at 100°C to give an amorphous yellow powder, MP 290°C to 291°C (with decomp.). 588 g of the embonate was dissolved in boiling water (4 liters).
Hydrobromic acid 50% w/w (325 g) diluted with water (2 liters) was added slowly at the boil and the precipitated embonic acid removed by filtering hot and washing twice with hot water (1 liter). The filtrate and washings were evaporated to dryness in a steam pan and the residue recrystallized from ethyl alcohol (1,200 ml), to yield the dibromide (320 g).

Antihypertensive

Hexamethonium bromide is a nicotinic acetylcholine receptor (nAChR) antagonist. It preferentially blocks nicotinic receptors at autonomic ganglia. It can cross the blood-brain barrier only at high doses.

[1] J A GOSLING  T C L. Uptake and distribution of some quaternary ammonium compounds in the central nervous system of the rat.[J]. Journal of Pharmacology and Experimental Therapeutics, 1969, 167 1: 56-62.
[2] D N MCKINSTRY  G B K. Effects of drugs on acetylcholine release from the cat superior cervical ganglion by carbachol and by preganglionic stimulation.[J]. Journal of Pharmacology and Experimental Therapeutics, 1967, 157 2: 328-336.
[3] YASUHIRO NISHIDA. Long-term blood pressure control: is there a set-point in the brain?[J]. Journal of Physiological Sciences, 2012, 62 3: 147-161. DOI: 10.1007/s12576-012-0192-0
[4] DAVID H MALIN . Nicotine Abstinence Syndrome Precipitated by Central But Not Peripheral Hexamethonium[J]. Pharmacology Biochemistry and Behavior, 1997, 58 3: Pages 695-699. DOI: 10.1016/s0091-3057(97)90006-x