Effect of Serotonin Inhibitors on Connective Tissue Disease

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SEROTONIN, histamine, and norepinephrine are highly active biologic substances, widely distributed in the body, and capable of producing various pharmacologic actions. The primary function of serotonin is not known, but like norepinephrine, it is believed to play an important role as a mediator of nerve impulses in certain regions of the body. Serotonin has been implicated in allergic and anaphylactic reactions, as has histamine. The metabolic pathways for these amines are well established, but little is known about the basic intracellular events that control their synthesis, storage, release, destruction, and their interaction with various hormones. Experiments have been reported which indicate that serotonin may increase tissue permeability, may cause inflammation, may stimulate fibrous proliferation, may induce vasomotor reactions, and may provoke pain when injected into certain tissues. Local injection of serotonin into the rat’s paw produces edema similar to that produced by histamine.1 Serial injections of serotonin into the subcutaneous tissue of the rat result in local progressive collagenous and fibrous tissue proliferation within the dermis.2 Injections of histamine into periarticular tissue of guinea pigs bring about inflammation and fibrosis of connective tissue.3

Certain clinical observations suggest also that these tissue mediators may affect the connective tissue system. The syndrome of malignant carcinoid, associated with increased amounts of serotonin and related substances, may be associated with fibroblastic proliferation of heart valves4 and rheumatic manifestations, or with skin and connective tissue changes suggestive of scleroderma.5 Recently we have observed a patient with malignant carcinoid in whom arthritis of the rheumatoid type. . .



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