Absence of neurotoxicity with medicinal grade terbutaline in the rat model

Reprod Toxicol. 2011 May;31(4):447-53. doi: 10.1016/j.reprotox.2011.01.001. Epub 2011 Jan 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / chemistry
  • Adrenergic beta-2 Receptor Agonists / toxicity*
  • Age Factors
  • Aging
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / pathology
  • Brain / physiopathology
  • Female
  • Male
  • Mass Spectrometry
  • Motor Activity / drug effects
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / physiopathology
  • Postural Balance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Terbutaline / chemistry
  • Terbutaline / toxicity*
  • Tocolytic Agents / chemistry
  • Tocolytic Agents / toxicity*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Tocolytic Agents
  • Terbutaline