The assessment of the behavioural teratogenic risk of the tocolytic drug phenoterol.
Phenoterol, a tocolytic drug widely used in cases of imminent preterm labour for disruption of uterine contractions, was studied for potential harmful impact on the developing fetal brain which is just going through the vulnerable period of accelerated histogenesis and cytodifferentiation. As the developmental stage of human fetus brain in late pregnancy closely resembles the ontogenetic phase of the rat brain in the early postnatal period, the model experiments were carried out using the drug administration in the neonate rat and life-long comprehensive follow-up of sequels in behaviour, reproductive functions and brain biochemical parameters. No deviations were found when phenoterol was administered in the dose 1 mg/kg/day s.c. on the postnatal days 6-9 (clinically relevant dosage). Several minor aberrations were observed after 10 times higher dose (10 mg/kg/day s.c. on postnatal days 5-7) in preweaning period (acceleration of somatic development) and in adulthood i.e. at the age of 2-7 months (higher score of emotionality). The inferiority of phenoterol treated rats became apparent only with the onset of senescence (age 11-14 months) when lower score of memory acquisition was ascertained joined with an increase of lipid peroxidation in the brain cortex.
Tejkalová
H
H
Psychiatric Research Institute, Czechoslovak Acad. Sci., Prague.
Benesová
O
O
Kristofíková
Z
Z
Binková
B
B
Dlohozková
N
N
Buresová
M
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005260:Female; D005280:Fenoterol / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D005280:Fenoterol; D003345:Corticosterone