Effects of an antagonist of neurokinin receptors 1, 2 and 3 on reproductive hormones in male beagle dogs

Brian P. Enright; Michael W. Leach; Georges Pelletier; Fernand LaBrie; Barry S. McIntyre; Patricia E. Losco

doi:10.1002/bdrb.20274

Effects of an antagonist of neurokinin receptors 1, 2 and 3 on reproductive hormones in male beagle dogs

Birth Defects Research Part B Developmental and Reproductive Toxicology ◽

10.1002/bdrb.20274 ◽

2010 ◽

Vol 89 (6) ◽

pp. 517-525 ◽

Cited By ~ 3

Author(s):

Brian P. Enright ◽

Michael W. Leach ◽

Georges Pelletier ◽

Fernand LaBrie ◽

Barry S. McIntyre ◽

...

Keyword(s):

Reproductive Hormones ◽

Beagle Dogs ◽

Neurokinin Receptors

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Administration of an Antagonist of Neurokinin Receptors 1, 2, and 3 Results in Reproductive Tract Changes in Beagle Dogs, but Not Rats

Toxicologic Pathology ◽

10.1080/01926230701198766 ◽

2007 ◽

Vol 35 (2) ◽

pp. 310-322 ◽

Cited By ~ 12

Author(s):

Patricia E. Losco ◽

Michael W. Leach ◽

Dineshwar Sinha ◽

Preston Davis ◽

Theodore J. Schmahai ◽

...

Keyword(s):

Reproductive Tract ◽

Beagle Dogs ◽

Neurokinin Receptors

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The Clinical, Roentgenological and Morphological Effects of an Acute Exposure of Phosgene on the Lungs of Dogs

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100065237 ◽

1971 ◽

Vol 29 ◽

pp. 236-237

Author(s):

R. F. Bils ◽

W. F. Diller ◽

F. Huth

Keyword(s):

Latent Period ◽

Chemical Industry ◽

Toxic Substance ◽

Lung Edema ◽

X Rays ◽

Beagle Dogs ◽

Male And Female ◽

Morphological Alterations ◽

Before And After ◽

Electron Microscopes

Phosgene still plays an important role as a toxic substance in the chemical industry. Thiess (1968) recently reported observations on numerous cases of phosgene poisoning. A serious difficulty in the clinical handling of phosgene poisoning cases is a relatively long latent period, up to 12 hours, with no obvious signs of severity. At about 12 hours heavy lung edema appears suddenly, however changes can be seen in routine X-rays taken after only a few hours' exposure (Diller et al., 1969). This study was undertaken to correlate these early changes seen by the roengenologist with morphological alterations in the lungs seen in the'light and electron microscopes.Forty-two adult male and female Beagle dogs were selected for these exposure experiments. Treated animals were exposed to 94.5-107-5 ppm phosgene for 10 min. in a 15 m3 chamber. Roentgenograms were made of the thorax of each animal before and after exposure, up to 24 hrs.

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Intraneuronal accumulations of lysosomes in the cerebellum of rats and dogs after dosing with MDL-832

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100161710 ◽

1990 ◽

Vol 48 (3) ◽

pp. 830-831

Author(s):

S.D. Barnard ◽

S.D. Warner

Keyword(s):

Brown Pigment ◽

Beagle Dogs ◽

Sprague Dawley ◽

Gelatin Capsules ◽

Pigment Granules ◽

Sprague Dawley Rats ◽

Hematoxylin And Eosin ◽

Dose Levels

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.

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Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159412 ◽

1990 ◽

Vol 48 (3) ◽

pp. 374-375

Author(s):

D.E. Loudy ◽

J. Sprinkle-Cavallo ◽

J.T. Yarrington ◽

F.Y. Thompson ◽

J.P. Gibson

Keyword(s):

Antidepressant Drug ◽

Beagle Dogs ◽

Long Term Effects ◽

Short Term ◽

Platelet Counts ◽

Toxicological Studies ◽

Induced Aggregation ◽

Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

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