Meprobamate

[3][4] However, three major drawbacks existed to the use of mephenesin as a tranquilizer: a very short duration of action, greater effect on the spinal cord than on the brain (resulting in a very low therapeutic index), and a weak activity.

[5] In May 1950, after moving to Carter Products in New Jersey, Berger and a chemist, Bernard John Ludwig, synthesized a chemically related tranquilizing compound, meprobamate, that overcame these three drawbacks.

Launched in 1955, it rapidly became the first blockbuster psychotropic drug in American history, becoming popular in Hollywood and gaining fame for its seemingly miraculous effects.

The disclosures came at a special scientific meeting at the Barbizon Plaza Hotel in New York City, at which Aldous Huxley addressed an evening session.

Meprobamate binds to GABAA receptors[21][22] which interrupts neuronal communication in the reticular formation and spinal cord, causing sedation and altered perception of pain.

[21] This relatively unique property makes meprobamate exceptionally dangerous when used in combination with other GABA-mediated drugs (including alcohol).

Symptoms of meprobamate overdose include drowsiness, headache, sluggishness, unresponsiveness, or coma; loss of muscle control; severe impairment or cessation of breathing; or shock.

With protracted use, it can cause physical dependence and a potentially life-threatening abstinence syndrome similar to that of barbiturates and alcohol (delirium tremens).

For this reason, discontinuation is often achieved through an extended regimen of slowly decreasing doses over a period of weeks or even months.

Alternatively, the patient may be switched to a longer-acting gabaergic agent such as diazepam (in a manner similar to the use of methadone therapy for opiate addiction) before attempting tapering.

[29] "In the January 2008 issue of Drug Safety Update, a stop press article announced the recent European review of carisoprodol for which the Committee for Medicinal Products for Human Use concluded that the risks of treatment outweigh the benefits.

This review was triggered by concerns from the Norwegian Medical Agency that carisoprodol (converted to meprobamate after administration) was associated with increased risk of abuse, addiction, intoxication, and psychomotor impairment."

Informational material advertising the prescription of meprobamate to children for anxiety disorders , stammering , tics and tantrums .
Meprobamate synthesis: [ 31 ] [ 32 ] [ 33 ]