Thalidomide, unknown effects

Side effects that arise as a consequence of a known mechanism of action are plausible and the connection with drug ingestion is simple to recognize. It is more dif cult to detect unwanted effects that arise from an unknown action. Some compelling examples of these include fetal damage after intake of a hypnotic (thalidomide), pulmonary hypertension after appetite depressants, and fibrosis after antimigraine drugs. 

Thalidomide has significant teratogenic effects in humans, and it also affects the central and peripheral nervous systems through unknown mechanisms. Evidence of a toxic arene oxide metabolite is unsubstantiated. Thalidomide likely inhibits neutrophil chemotaxis and monocyte phagocytosis, inhibits free radical formation, and alters the ratio of helper and suppressor T-cells. Reduced formation of tissue necrosis factor-a may be at least partially responsible for the antiinflammatory effects of thalidomide. 

Figure 8-12 Pharmacological effects elicited by thalidomide and their possible target phenomena/molecules (a) established or possible target (b) major contribution (c) partial contribution (d) minor or unknown contribntion.

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