The drug was introduced in 1957 in Germany and April 1958 in the UK. Several doctors in Germany (Lenz), UK (Speirs) and Australia (McBride) began noticing limb deformities and began to suspect thalidomide might be responsible. It was withdrawn from use in the UK in November 1961.
Thalidomide left a legacy of thousands of 'thalidomide babies' who were born with severe birth defects, particularly involving abnormal limb development. This was observed in several countries around the world with the exception of the USA, where the US Food and Drug Administration (FDA) refused approval because of the neuropathy associated with its use.
The lessons from thalidomide led to a much more cautious approach to prescribing in pregnancy. Several medications appear to have a safe profile in pregnancy and are routinely used in obstetrics (e.g. opioids and certain antibiotics). However, most other drugs are generally avoided if at all possible, even in the absence of adverse teratogenic effects in experimental conditions.
Thalidomide has anti-angiogenic properties probably mediated by its function as an inhibitor of basic fibroblast growth factor-2 (bFGF) and immuno-modulatory effects as it is a tumour necrosis factor alpha (TNF-α) inhibitor . Thalidomide and chemical derivatives of thalidomide now have a role in treatment of multiple myeloma.
- It should no longer be used in leprosy as both steroids and more importantly clofazimine are more effective without the potential for misuse in women of childbearing age(WHO recommendation)
- In 2008 The European Medicines Agency (EMEA) has recommended that it can be relicensed for multiple myeloma. The precautions recommended include particular information leaflets for both male and female users, and might be thus seen medicolegally as the minimum standard of information that should be given to patients.
- R-thalidomide is sedative and an inhibitor of inhibitor of basic fibroblast growth factor-2 (bFGF) and tumour necrosis factor alpha (TNF-α)
- S-thalidomide is teratogenic, although the mechanism is still poorly understood. A thalidomide binding protein, cereblon (CRBN) may have a key role. Thalidomide inhibits the activity of the redox-sensitive transcription factor NF-κB, shifts the balance of growth factors towards pro-apoptotic bone morphogenetic proteins, and suppresses Wnt/β-catenin and Akt-dependent survival signalling in the limb bud.
It is pointless using pure R-thalidomide as a safe drug as enzymatic transformation in humans produces some S-thalidomide from R-thalidomide.
- ↑ SPEIRS AL. Thalidomide and congenital abnormalities. Lancet. 1962 Feb 10; 1(7224):303-5.
- ↑ McBride WG. Thalidomide and congenital abnormalities. Lancet. 1962 2:1358. Link to image of letter on James Lind Library
- ↑ Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. The New England journal of medicine. 1999 Nov 18; 341(21):1565-71.
- ↑ Juliusson G, Celsing F, Turesson I, Lenhoff S, Adriansson M, Malm C. Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma. Br J Haematol. 2000 Apr;109(1):89-96.
- ↑ Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004 Apr;4(4):314-22
- ↑ Supply of unlicensed Thalidomide products in the UK. MHRA 08 Dec. 2008 -Letter to NHS Prescription Services
- ↑ Ito T, Ando H, Handa H. Teratogenic effects of thalidomide: molecular mechanisms. Cellular and molecular life sciences : CMLS. 2011 May; 68(9):1569-79.(Link to article – subscription may be required.)
- ↑ Knobloch J, Jungck D, Koch A. Apoptosis induction by thalidomide: critical for limb teratogenicity but therapeutic potential in idiopathic pulmonary fibrosis? Current molecular pharmacology. 2011 Jan; 4(1):26-61.