Protective activity of ketanserin against serotonin‐induced embryotoxicity and teratogenicity in rats

Abstract

Van Cauteren, H., J. Vandenberghe, and R. Marsboom: Protective activity of ketanserin against serotonin-induced embryotoxicity and teratogenicity in rats. Drug Dev. Res. 8: 179-1 85, 1986. Serotonin was evaluated for its embryotoxic and teratogenic effects in pregnant Wistar rats at total doses of 10, 15, and 20 mg/kg divided over five injections at day 9 to 11 of pregnancy. At day 22 of pregnancy, rats were sacrificed and examined for number of live, dead, and resorbed fetuses and mean pup weight. Teratological evaluation was carried out by visual inspection, radiography, and sectioning according to Wilson's technique. When compared to placebo controls, serotonin resulted in dose-dependent embryotoxicity as evidenced by increased embryonal resorption and decreased pup weight. Furthermore, serotonin dose-dependently induced malformations, which were mainly acrania, encephalocele, hydrocephalocele, cheiloschisis, coelosomia, and rib abnormalities. Ketanserin, when given orally at a dose level of 5 mg/kg 1 hour before each serotonin injection, completely prevented the serotonin-induced embryotoxicity and teratogenicity.

Pregnancy Complications and Neonatal Mortality in a Serotonin Transporter Null Mouse Model: Insight Into the Use of Selective Serotonin Reuptake Inhibitor During Pregnancy

“…Therefore, lack of SERT ( Sert−/− ) or pharmacological inhibition of SERT (SSRI treatment) results in increased plasma concentrations of serotonin ( 9 , 25 , 26 ). Previous studies using 5-HTP (serotonin precursor) to elevate circulating serotonin have observed reduced uterine/placental blood perfusion and increased pregnancy loss ( 27 , 28 ). This is consistent with the decrease in uterine artery blood flow that has been observed during SSRI treatment ( 29 ).…”

Mouse 5‐HT2B Receptor‐mediated Serotonin Trophic Functionsa

“…2 Furthermore, 5‐HT has been shown to affect rat, mouse, and chicken morphogenesis. 3–5 Some of these effects have been reported to be mediated by 5‐HT 2 ‐like receptors. 3,4 5‐HT, which is detected during mammalian embryonic development before nervous system differentiation, is probably from maternal origin.…”

“…3–5 Some of these effects have been reported to be mediated by 5‐HT 2 ‐like receptors. 3,4 5‐HT, which is detected during mammalian embryonic development before nervous system differentiation, is probably from maternal origin. 5‐HT has been shown to participate in morphogenesis, 2 by acting, among various developmental signals, on mouse cranial neural crest (NC) migration.…”

5-HT2B receptor-mediated serotonin morphogenetic functions in mouse cranial neural crest and myocardiac cells

“…in the neuroepithelium and myocardium (Shuey et al, 1993). Furthermore, 5-HT has been shown to affect rat and mouse cranio-facial (Van Cauteren et al, 1986;Shuey et al, 1993) and chicken and mouse cardio-vascular morphogenesis (Huether et al, 1992;Yavarone et al, 1993b). Some of these effects have been reported to be mediated by 5-HT2-like receptors (Van Cauteren et al, 1986;Huether et al, 1992).…”

“…These malformations overlap those observed in whole embryo culture following exposure of mouse embryos to 13-cis-retinoic acid (Lauder, 1988;. 5-HT has also been shown to participate in rat cranio-facial development (Van Cauteren et al, 1986) and to be involved in the formation and migration of the cranial neural crest (NC) cells (Moiseiwitsch and Lauder, 1995) as well as in chicken and mouse cardio-vascular morphogenesis (Huether et al, 1992;Yavarone et al, 1993b).…”