
<b>Chemistry </b>
Thalidomide is a synthetic glutamic acid derivative. The drug is structurally similar to glutethimide, and that similarity may be responsible for its sedative and hypnotic effects.

Thalidomide occurs as a white to off-white, nearly odorless, crystalline powder. 
Commercially available thalidomide capsules should be stored at 15--30 C and protected from light. In vitro in whole blood, serum, or plasma, thalidomide undergoes spontaneous hydrolysis. The rate of hydrolysis of thalidomide increases with pH over the range of 7--7.5. 

<b>Actions</b>
Thalidomide is an immunomodulatory agent with anti-inflammatory activity. The drug also has anti-angiogenic effects and sedative and hypnotic effects. 


<b>Immunomodulatory Effects </b>
The mechanism(s) of action of the immunomodulatory and anti-inflammatory effects of thalidomide are complex and have not been fully determined.  It is suggested that there are some interactions with tumor necrosis factor alpha (TNF-alpha) levels, T-cells, interleukin-2, interferon-Gamma, and/or leukocyte migration and chemotaxis. medscape

The immunomodulatory and anti-inflammatory effects of thalidomide differ from those of other immunosuppressive agents, including corticosteroids, cyclosporin, macrolide immunosuppressants, pentoxifylline, immunosuppressive purine analogs and purine metabolism inhibitors, and also differ from those of nonsteroidal anti-inflammatory agents.
Thalidomide does not appear to interfere with important host germ fighting mechanisms; and has no direct antibacterial activity in those bacterial diseases where it is effective.

<b>Effects on Angiogenesis</b> 
Thalidomide inhibits angiogenesis, and it has been suggested that the prevention of growth on fetal limbs may be related to inhibition of blood vessel growth. Thalidomide's anti-angiogenic effects have been demonstrated in several animal angiogenesis models; however, there is evidence that the drug's antiangiogenic effects may be species specific and possibly may be related to a species-specific metabolite and/or metabolic activation. 
The mechanism of thalidomide's antiangiogenic effects is unknown. 

<b>Sedative and Hypnotic Effects</b> 
Thalidomide has CNS depressant effects and causes sedation. The drug has a prompt sedative effect, and does not cause a hangover. The glutarimide ring contained in thalidomide appears to be responsible for the sedative and hypnotic effects of the drug; the ring is structurally similar to ring moieties contained in some other sedative and hypnotic drugs. Thalidomide may activate a sleep center in the forebrain, a mechanism of action unlike that of barbiturates. 
Thalidomide has little acute CNS toxicity, and does not cause incoordination or respiratory depression even at large doses. While thalidomide initially was investigated for use as a sedative and hypnotic in the late 1950s, the drug is no longer promoted for use as a sedative and hypnotic because of the risk to developing fetuses.  One does not want this drug to seep into the general water supply.

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