The theory of neurohumoral transmission received direct experimental validation nearly a century ago (see von Euler , 1981 ), and extensive investigation during the ensuing years led to its general acceptance. Nerves transmit information across most synapses and neuroeffector junctions by means of specific chemical agents known as neurohumoral transmitters or, more simply, neurotransmitters. The actions of many drugs that affect smooth muscle, cardiac muscle, and gland cells can be understood and classified in terms of their mimicking or modifying the actions of the neurotransmitters released by the autonomic fibers at either ganglia or effector cells | are usually mild and transient, although drug withdrawal is infrequently required to reverse more severe reactions. Common side effects consist of gastrointestinal disturbances, including heartburn, diarrhea, cramps, nausea, and vomiting, and symptoms related to vasospasm-induced ischemia (numbness and tingling of extremities, pain in the extremities, low back and abdominal pain). Effects attributable to central actions include unsteadiness, drowsiness, weakness, lightheadedness, nervousness, insomnia, confusion, excitement, hallucinations, and even frank psychotic episodes. Reactions suggestive of vascular insufficiency have been observed in a few patients, as well as exacerbation of angina pectoris. A potentially serious complication of prolonged treatment is inflammatory fibrosis, giving rise to various syndromes, including retroperitoneal fibrosis, pleuropulmonary fibrosis, and coronary and endocardial fibrosis. Usually the fibrosis regresses after drug withdrawal, although persistent cardiac valvular damage has been reported. Because of this danger, other drugs are preferred for the prophylactic treatment of migraine.
