Teratogenicity mechanisms

This information suggests that early pharmacological REM sleep suppression or other types of state disorganization may disrupt brain and behavioral development. Behavior in adulthood may still be changed as a consequence of the abnormal development, but also as a result of the aberrant adult sleep pattern. Therefore, chronic early REM sleep-like state suppression or other types of state disorganization may be important neurobehavioral teratogenic mechanisms (see also refs. 77, 118, 129). 

The risk of foetal malformation is increased in women with epilepsy compared with the general population. Minor dysmorphic features are most frequent, but more severe forms such as facial clefts and neural tube defects are not uncommon. The two major forms of neural tube defects are (i) anence-phaly, a lethal malformation, and (ii) spina bifida—a closure defect in the spinal eolumn that may lead to paralysis of the lower limbs. The rates of malformations are about 3% with CBZ and lamotrigine (LTG), 7% with VPA, and 15% with combinations of two or more AEDs. It is probable that AEDs have several different teratogenic mechanisms. Low folate levels appear to be associated with increased risks of foetal malformations in women on AEDs. Furthermore, it has been suggested that maternal C677T MTHFR polymorphism or some abnormality related to methionine synthetase increase the risk of foetal malformation in patients on AEDs (Mills et al. 1995). 

Thalidomide Polycyclic teratogen, antiangiogenic mechanism unknown... 

Miltefosine, an alkylphosphocholine derivative, is a new antileishmanial drug and the first effective oral treatment of visceral leishmaniasis. However, there are concerns regarding teratogenicity, rapid emergence of resistance, and variable cure rates, possibly due to species differences in drug sensitivity. The mechanism of action of miltefosine is not known. 

Beckman, D. A. and Brent, R.L. (1986). Mechanism of known environmental teratogens drugs and chemicals. Clin. Perinatal. 13 649-687. 

PASS Predicts 900 pharmacological effects, mechanisms of action, mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity... 

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