Valium (Diazepam) - Description and Clinical Pharmacology

DESCRIPTION:

Valium (diazepam) is a benzodiazepine derivative. The chemical name of diazepam is 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one. It is a colorless to light yellow crystalline compound, insoluble in water. The empirical formula is C₁₆H₁₃ClN₂O and the molecular weight is 284.75. The structural formula is as follows:

Valium is available for oral administration as tablets containing 2 mg, 5 mg or 10 mg diazepam. In addition to the active ingredient diazepam, each tablet contains the following inactive ingredients: anhydrous lactose, corn starch, pregelatinized starch and calcium stearate with the following dyes: 5-mg tablets contain FD&C Yellow No. 6 and D&C Yellow No. 10; 10-mg tablets contain FD&C Blue No. 1. Valium 2-mg tablets contain no dye.

PHARMACOLOGY:

In animals, Valium appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Valium, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with Valium do have a transient ataxia at higher doses. Valium was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function.

Oral LD₅₀ of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. Intraperitoneal administration of 400 mg/kg to a monkey resulted in death on the sixth day.

Reproduction Studies:

A series of rat reproduction studies was performed with diazepam in oral doses of 1, 10, 80 and 100 mg/kg. At 100 mg/kg there was a decrease in the number of pregnancies and surviving offspring in these rats. Neonatal survival of rats at doses lower than 100 mg/kg was within normal limits. Several neonates in these rat reproduction studies showed skeletal or other defects. Further studies in rats at doses up to and including 80 mg/kg/day did not reveal teratological effects on the offspring.

In humans, measurable blood levels of Valium were obtained in maternal and cord blood, indicating placental transfer of the drug.