Improved methodology for identifying the teratogenic potential in early drug development of hERG channel blocking drugs

Nilsson, Mats F. (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Toxikologi

Danielsson, C. (author)

Sköld, A.-C. (author)

Johansson, A. (author)

Blomgren, B. (author)

Wilson, J. (author)

Khan Niazi, Khalid Muhammad (author): Uppsala universitet,Centrum för bildanalys,Datoriserad bildanalys

Bengtsson, Ewert (author): Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Datoriserad bildanalys,Centrum för bildanalys,Centre for Image Analysis

Kultima, Kim (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för medicinska vetenskaper,Toxikologi

Webster, W. S. (author)

Danielsson, Bengt R. (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Toxikologi

(creator_code:org_t)

Elsevier, 2010
2010
English.
In: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 29:2, s. 156-163

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; https://res.slu.se/i...; show less...

Abstract Subject headings

Drugs blocking the potassium current IKr of the heart (via hERG channel-inhibition) have the potential to cause hypoxia-related teratogenic effects. However, this activity may be missed in conventional teratology studies because repeat dosing may cause resorptions. The aim of the present study was to investigate an alternative protocol to reveal the teratogenic potential of IKr-blocking drugs. The IKr blocker astemizole, given as a single dose (80mg/kg) on gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart rate at 20nM, and arrhythmias at 200-400nM. Cetirizine, without IKr-blocking properties, did not affect the rat embryonic heart in vitro. The present study shows that single dose testing on sensitive days of development, together with whole embryo culture, can be a useful methodology to better characterize the teratogenic potential of IKr-blocking drugs.

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
NATURVETENSKAP -- Data- och informationsvetenskap -- Datorseende och robotik (hsv//swe)
NATURAL SCIENCES -- Computer and Information Sciences -- Computer Vision and Robotics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

By the author/editor: Nilsson, Mats F.; Danielsson, C.; Sköld, A.-C.; Johansson, A.; Blomgren, B.; Wilson, J.; show more...; Khan Niazi, Khal ...; Bengtsson, Ewert; Kultima, Kim; Webster, W. S.; Danielsson, Beng ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

NATURAL SCIENCES: NATURAL SCIENCES; and Computer and Inf ...; and Computer Vision ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Other Clinical M ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

By the university: Uppsala University; Karolinska Institutet; Swedish University of Agricultural Sciences

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