The pre- and post-natal toxicity of penequine hydrochloride in mice.
Penequine hydrochloride, a novel anticholinergic agent, was developed as an effective treatment for organophosphorus intoxication (e.g., soman poisoning). The current study was performed to assess the potential pre- and post-natal toxicity of penequine hydrochloride in mice. Approximately 120 timed-pregnant mice were assigned to four dose groups (n=30 per group). Dams were exposed orally to 0, 2.5, 12.5, 62.5 mg/L penequine hydrochloride in drinking water from gestation day 6 to lactation day 21. The F1 generation mice, which were not exposed directly to penequine hydrochloride as pups or as adults, were bred to produce F2 generation fetuses for the fertility test of the F1 population. Various pre- and post-natal measurements, including neurobehavioral tests, were performed with the F0 and F1 mice. Among the significant findings were decreases in water consumption, viability, organ weights and delay of physical landmarks in 62.5 mg/L groups. With the exception of treatment-unrelated abnormality in surface righting reflex in the F1 generation, penequine hydrochloride did not produce any adverse effects at doses up to and including 12.5 mg/L (equal to 2.5 mg/kg/day in mice) that were at least 75 times of human therapeutic dosage.
Zhang
Zibo
Z
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Xuan Wu District, Beijing, China.
Zhang
Qinglin
Q
Huang
Chunqian
C
Jin
Hongtao
H
Wang
Zhiqiao
Z
Wang
Aiping
A
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000633:toxicity; D003517:Cyclopentanes / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D011812:Quinuclidines / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
D018680:Cholinergic Antagonists; D003517:Cyclopentanes; D011812:Quinuclidines; C066419:3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyethoxy)quinuclidine