The road to tranquility: the search for selective anti-anxiety agents

The earliest treatments of anxiety included cathartics and emetics, which were used to remove the excess of black bile (hence our word melancholia) thought to be responsible for the patient's demeanor. By the 1700s, physicians were prescribing drugs that are more selective for the CNS, chiefly opium and strengthening tonics. In the 1860s, cardioactive drugs such as atropine, aconite, and digitalis were assumed to counteract anxiety because it could be associated with tachycardia and/or melancholia. A little later, the emergence of laboratory animal models, culminating in the conditioned avoidance response, and also Freudian psychiatry, permitted the evolution of new definitions of anxiety, as well as the introduction of sedative agents such as KBr, chloral hydrate, and barbiturates for its treatment. The first somewhat selective anxiolytics, reserpine, meprobamate, and chlorpromazine, appeared in the early 1950s, while in 1959 the benzodiazepines were the first to prove more selective than all the others in a systematic battery of screening tests.