midazolam

midazolam, drug used to induce general anesthesia, to reduce anxiety during medical procedures, and to treat acute and severe seizures. Midazolam is classified as a benzodiazepine drug, owing to its core chemical structure (a benzene ring fused with a diazepine ring) and its ability to produce a calming, sedative effect; its rapid onset and short duration of action make it unique among benzodiazepines. Midazolam is marketed under various brand names, including Dormonid, Dormicum, Hypnovel, and Versed.

Midazolam was first synthesized in the mid-1970s by American researchers Armin Walser and Rodney Fryer at the biotechnology and pharmaceutical company Hoffmann-La Roche. The company patented the drug in 1976. It was first approved by the U.S. Food and Drug Administration (FDA) in 1985 for the induction of anesthesia and sedation. The drug found use in a variety of diagnostic and therapeutic situations, particularly for procedures in the areas of dentistry, oncology, and cardiac surgery. In 2018 an intramuscular formulation of midazolam was approved by the FDA for use in adults who experience status epilepticus (a form of severe seizure). The following year, a nasal spray preparation was approved for the treatment of acute seizure in patients age 12 or older. Midazolam is also sometimes used in the palliative care of terminally ill patients.

Midazolam exerts its effects on the central nervous system, where it binds to a unique site on gamma-aminobutyric acid A (GABA_A) receptors and thereby augments activity of the inhibitory neurotransmitter GABA. Increased GABA activity causes skeletal muscles to relax and decreases neural transmission in the brain, producing an overall calming effect and inducing sleep. Midazolam may be administered orally or nasally or be injected intramuscularly, intravenously, or subcutaneously. Regardless of the route of administration, the drug is absorbed rapidly, with onset of effects occurring within minutes.

Side effects of midazolam are generally associated with its sedative actions and may include anxiety, confusion, irregular heartbeat, shallow breathing, decreased blood pressure, restlessness, and weakness. In instances of overdose, patients may experience decreased reflexes, loss of coordination, respiratory depression, sleepiness, and loss of consciousness. In rare instances, severe suppression of cardiovascular and respiratory function can result in permanent neurological damage or death. Repeated or long-term use of midazolam, such as in palliative care settings, may lead to tolerance, and withdrawal syndrome may result when such use is abruptly reduced or discontinued.