Relationship between teratogeny and structure in the thalidomide field

Wuest, H; Fox, R. R.; Crary, D. D.

doi:10.1007/bf02138700

Cited by 24 publications

(4 citation statements)

References 8 publications

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“…This observation suggests that embryotoxic thalidomide derivatives contain an intact phthalimide moiety. However, several thalidomide analogues containing substituted phthalimide moieties were found to be nonteratogenic (Fabro et al 1964;Smith et al 1965;Williams 1968;Wuest et al 1968), demonstrating that the structure of the glutarimide part of the molecule is related to the biological activity of the compound. EM 12 has been used as a treatment for ENL with unsatisfactory results (Sheskin 1978).…”

Section: The Role Of Hydrolysis Productsmentioning

confidence: 97%

Thalidomide in Human Immunodeficiency Virus (HIV) Patients

Günzler¹

1992

Drug Safety

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The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects. The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy. This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity. The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients. This article reviews the most important chemical and pharmacokinetic properties of thalidomide. The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed. Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded. Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy. Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups. Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age. Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded. Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy. In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy.

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Section: The Role Of Hydrolysis Productsmentioning

confidence: 97%

Thalidomide in Human Immunodeficiency Virus (HIV) Patients

Günzler¹

1992

Drug Safety

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“…Thalidomide analogue EM255 [12] 3-(1-Oxo-1,3-dihydro-2H-isoindol-2-yl) piperidine-2-one Rabbit 37 Table 5 shows 16 compounds (compounds 33-48) in which the phthalimide ring has been left intact with structural modification or replacement of the glutarimido ring. 34,43,47,[50][51][52] All compounds were inactive as teratogens in the pregnant rabbit and two of these chemicals are used as pesticides (compounds 36, 37). The negative findings for N-hydroxythalidomide (com- α-Aminoglutarimide [19] 3-Aminopiperidine-2,6-dione Rabbit 33,42 L-Glutamine [20] ( 2 S)-2,5-Diamino-5-oxopentanoic acid Rabbit 33,42 DL-Glutamine [21] 2,5-Diamino-5-oxopentanoic acid Rabbit 33,42 Phthalic acid [22] Benzene-1,2-dicarboxylic acid Rabbit 33,42 Toxicology Research Review pound 43) and N-methoxythalidomide (compound 44) were a little surprising considering they possess only minor additions to the glutarimido ring, but these observations might be explained if they were to undergo a rapid conjugation with glucuronic acid, the latter after demethylation.…”

Section: Rabbit 37mentioning

confidence: 99%

Thalidomide-type teratogenicity: structure–activity relationships for congeners

Smith

Mitchell

2018

Toxicology Research

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“…Earlier reviews (1)(2)(3)(4)(5)(6)(7)(8) discussed the teratogenic effects of some of the phthalates and related chemicals. Though PAEs in general seem to require high doses to trigger embryotoxic actions, some appear to be more teratogenic than others.…”

Section: Teratologymentioning

confidence: 99%

Effects of Phthalic Acid Esters (PAEs) on the Neonate and Aspects of Teratogenic Actions

Thomas¹,

Wienckowski²,

Gillies³

et al. 1986

Environmental Health Perspectives

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A review of the literature reveals that several different phthalic acid esters (PAEs) are capable of causing testicular damage. Phthalate-induced zinc deficiency is consistent with germinal epithelial damage. Among experimental animals, mice perhaps show the greatest sensitivity to phthalate-induced terata, but high doses/exposure are required. Little toxicologic information is available with regard to phthalate-induced effects upon the neonate.

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Relationship between teratogeny and structure in the thalidomide field

Cited by 24 publications

References 8 publications

Thalidomide in Human Immunodeficiency Virus (HIV) Patients

Thalidomide in Human Immunodeficiency Virus (HIV) Patients

Thalidomide-type teratogenicity: structure–activity relationships for congeners

Effects of Phthalic Acid Esters (PAEs) on the Neonate and Aspects of Teratogenic Actions

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