A number of studies have been performed, which are relevant to the question of whether diazepam has any action in organophosphate poisoning other than as an anticonvulsant. These studies have concentrated on various aspects of the cholinergic system, as well as the GABAergic system and cGMP concentrations. Very large doses of diazepam (20 mg/kg), increased the acetylcholine content of mouse brain (Tonkopii et al., 1978). In the corpus striatum and hippocampus of rats exposed to sarin and soman, diazepam decreased the magnitude of the elevations in choline concentrations, but not those of acetylcholine (Flynn & Wecker, 1986). On the basis of studies on the acetylcholine synthetic system of the mouse brain, Lundgren et al. (1987) suggested that in addition to observed effects on acetylcholine turnover, diazepam might have an effect on choline transport across the blood-brain barrier. Whether diazepam-induced effects on the GABAergic system are responsible for anticonvulsant activity in soman poisoning is unresolved (Lundy et al., 1978). An effect on soman-induced elevations in central nervous cGMP concentrations has been hypothesized as a mechanism of action of the benzodiazepin
Diazepam commonly traded under the name Valium is one of the chemicals found in a large class of compounds known as Benzodiazepines. Benzodiazepines are mostly used as tranquilizers, skeletal muscle relaxants and anxiolytics. They have low toxicity as well as a wide variety of pharmacological profiles. Librium or Chlordiazepoxide was the first benzodiazepine to be synthesized. As a testing sample was submitted to carry out further testing, the establishment of this antibiotic was discovered by L. Sternbach and E. Reeder. In addition, during synthesis, the compound structure was determined to have Librium.
Diazepam then came shortly after the discovery of Librium. Synthesis of Diazepam is from an available starting material 5-chloroisatoic anhydride. Diazepam yield is around 50%.
Synthesis of diazepam starting with commercially available 5-chloroisatoic anhydride is the synthetic route mostly used because it gives the highest percentage yield of around 50%. Another reason is that 5-chloro-isatoic anhydride is easily available since it can be purchased.
5-chloro-n-methylisatoic anhydride (C9H6ClNO3):
Review on Synthesis of Biologically Active Diazepam Derivatives
Gogerty JH, Griot RG, Habeck D, Iorio LC, & Houlihan WJ (1977) Synthesis and central nervous system evaluation of some 6-alkoxy-3H-1,4-benzodiazepin-2(IH)-ones. J Med Chem, 20: 952-956.