Species Differences in Experimental Teratogenesis by Tranquillising Agents

Szabo, K. T.; Brent, RobertL.

doi:10.1016/s0140-6736(74)92749-4

Cited by 50 publications

(18 citation statements)

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“…The amount of this decrease is similar to the weight loss seen in rat pups severely undernourished in the neonatal period (Bedi et al, 1980b;Krigman and Hogan, 1976;Pascual-Leone et al, 1985;Wiggins and Fuller, 1978;Wiggins et al, 1984). It has been reported that thioridazine administration reduces food intake (Szabo and Brent, 1974). Undernourishment causes effects on myelination; these effects are well documented.…”

Section: Discussionsupporting

confidence: 57%

Inhibition of peroxisomal beta‐oxidation and brain development in rats

Branden

Dacremont²,

Hooghe

et al. 1989

Glia

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Thioridazine, an inhibitor of peroxisomal beta-oxidation, was administered orally to nursing rats during the period of maximal myelination in the pups (8-21 days postnatally). Under the experimental conditions, thioridazine causes accumulation of C24 and C26 fatty acids in pup brain lipids, an effect we consider to be a typical consequence of inhibited peroxisomal beta-oxidation. In the corpus callosum of treated pups, the relationship between axon diameter and myelin sheath thickness is altered compared with matched controls. Thioridazine also induces undernourishment effects in 21 day-old rats. Body and brain weight are severely reduced. Liver peroxisomes show a starvation-type metabolism. Undernourishment is known to influence myelination in developing rat brain. However, known consequences of undernourishment, such as decreased myelin concentration in whole brain, decreased percentage of myelinated fibers, and decreased granule-to-Purkinje cell ratio are not present.

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Section: Discussionsupporting

confidence: 57%

Inhibition of peroxisomal beta‐oxidation and brain development in rats

Branden

Dacremont²,

Hooghe

et al. 1989

Glia

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“…Several compounds can cause cleft palate in mice, without overt teratogenic activity in other species. These comprise, among others, fluphenazine, haloperidol, trifluperidol, and thioridazine (Vichi et al, 1968;Vichi, 1969;Szabo and Brent, 1974). Studies addressing phenothiazine teratogenicity in rats have yielded conflicting results (Jelinek et al, 1967;Clark et al, 1970;Beall, 1972;Singh and Padmanabam, 1978), whereas haloperidol causes increased incidence of fetal resorption, delayed delivery, and neonatal death at doses 2-to 10-fold higher than the maximum doses used in humans (Dollery, 1999).…”

Section: A Antipsychotic Drugsmentioning

confidence: 99%

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

2004

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“…Animal teratogenicity studies have also met with mixed results. For example, perphenazine causes cleft palate in mice and rats but not in rabbits [181] while CPZ causes cleft palate in mice [182]. Phenothiazines undergo extensive oxidative metabolism in human body.…”

Section: Drugsmentioning

confidence: 99%

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Kulkarni

2001

CPD

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Many developmental toxicants and teratogens require prior metabolism to reactive species or free radicals to exert toxicity. Thus the knowledge of conceptal biotransformation is absolutely critical in understanding toxicity of these chemicals. Due to extremely low content of cytochrome P450 in the embryo and other conceptal tissues, the research focus in recent years has steadily shifted toward enzymes capable of peroxidative oxidation of xenobiotics. At least three enzymes viz. lipoxygenase, peroxidase and prostaglandin synthase, each capable of peroxidative xenobiotic metabolism, occur in conceptal tissues of man and laboratory animals in biologically significant amounts. This review mainly summarizes the available information on the enzymatic bioactivation of teratogens and developmental toxicants belonging to diverse classes such as drugs, pesticides, environmental contaminants, industrial and other chemicals. Additionally, some discussion is devoted toward issues such as drug-drug interactions. The emerging new information on the peroxidative glutathione conjugate formation from xenobiotics is also presented. A critical need for gathering more information on this subject using different enzyme preparations from human conceptal tissues is stressed to avoid tragedies in the future.

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Species Differences in Experimental Teratogenesis by Tranquillising Agents

Cited by 50 publications

References 0 publications

Inhibition of peroxisomal beta‐oxidation and brain development in rats

Inhibition of peroxisomal beta‐oxidation and brain development in rats

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

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