Absence of neurotoxicity with medicinal grade terbutaline in the rat model.
To evaluate neurological effects of terbutaline, rats were injected with saline, terbutaline (Sigma or American Pharmaceutical Partners (APP™)) at 0.5 mg/kg-d or 10 mg/kg-d between postnatal days (PND) 2-5 or 11-14. Brains collected 24 h after last injection were used to determine corpus-callosum thickness, Purkinje cell and neuronal number in the cerebellum. Ambulation, distance traveled, resting time and time on rotarod were analyzed. Terbutaline (both doses/grades at PND 11-14) decreased corpus-callosum thickness. Ambulation time was significantly decreased in the 10 mg/kg-d (Sigma) and 0.5 mg/kg-d of terbutaline (APP™) (PND 2-5) juvenile-rats and 10 mg/kg-d-Sigma adult-rats, 0.5 mg/kg-d APP™ (PND 11-14) adult-rats. Resting time was increased in both doses of APP™ (PND 2-5) in juvenile-rats, 10 mg/kg-d Sigma adult-rats. 10 mg/kg-d-Sigma (PND 2-5) decreased distance traveled in adult-rats. 0.5 mg/kg-d-Sigma (PND 2-5 and PND 11-14) decreased the time spent on rotarod (30 RPM) in adult-rats. Sigma terbutaline Sigma had 2× as much free base compared to APP™. In conclusion, APP™ terbutaline did not have a deleterious effect on the developing rat brain.
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. myowens@umsmed.edu
Michelle Y
MY
Owens
Kedra L
KL
Wallace
Naila
N
Mamoon
Josephine
J
Wyatt-Ashmead
William A
WA
Bennett
D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry / Q000633:toxicity*; D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013726:Terbutaline / Q000737:chemistry / Q000633:toxicity*; D015149:Tocolytic Agents / Q000737:chemistry / Q000633:toxicity*
D058666:Adrenergic beta-2 Receptor Agonists; D015149:Tocolytic Agents; D013726:Terbutaline
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