Though many centuries ago clinical notes were taken and occasionally some experiments were made to discover the physiologic action of drugs, nothing scientific was accomplished or recorded until Magendie published his experiments, in 1816.
He found that strychnia in solution could be absorbed from mucous surfaces, rapidly from serous cavities, and slowly from an isolated loop of intestine. He proved by his famous experiment of dividing all of the structures of a dog's leg and connecting the severed ends of the main artery and vein with quills, and then injecting strychnia into this severed leg, that the convulsions caused by strychnia were due to the action of the drug on the central nervous system, which it reached through the blood. He next found that the nearer to the central nervous system the blood current was into which the strychnia was injected, the more quickly the convulsions developed.
Since convulsions may be caused by action of a drug on the brain, spinal cord, or muscles, Magendie's next problem was to prove on which part the strychnia acted. He first destroyed the spinal cord at the moment the poison was injected, and no convulsions occurred, thus demonstrating that the strychnia did not act upon the brain to cause convulsions. He next showed that while strychnia convulsions were occurring they could be stopped by passing a whalebone down the spinal canal, the convulsions ceasing in the parts of the body innervated by the section of the cord thus destroyed and continuing in the parts innervated from below such destruction.
Magendie then placed a little of a solution of strychnia on a portion of exposed spinal cord, and convulsions soon began, first in the parts of the body innervated by the section of the cord to which the poison was applied, and later, after absorption into the circulation had taken place, the convulsions became general.
In thus demonstrating that strychnia can be absorbed conveyed by the circulation, and act upon the motor tract of the spinal cord, Magendie has well earned the title of Nestor of Pharmacologic Research.
In 1884, Claude Bernard, a pupil of Magendie, published his classic investigations of the paralyzing power of curare on the terminal endings of the motor nerves. He showed that this drug is not very poisonous when administered by the stomach if the kidneys are intact, but that it causes general paralysis when injected into the tissues of the body. Bernard proved that curare acted principally upon the terminal endings of the motor nerves by ligating the artery and vein of one leg of a frog, and then injecting the poison under the skin of the back. The blood could distribute the curare into all parts of the body except the ligated leg. Irritation of any part of the frog caused movements only in the ligated leg, thus showing that the sensory nerves could transmit stimuli to the cord and the latter could reflexly transmit them to the motor nerves, but the only muscles that received the stimuli and contracted were those of the leg which the curare could not reach.
Following these early investigators is a long line of tireless workers who have scientifically developed our modern treatises on pharmacology and have taught clinicians to meet therapeutic indications rationally.