Fluoro-norchloroepibatidine: preclinical assessment of acute toxicity.
18Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 microg/kg; administered intravenously) resulted in 30% mortality. Neither 0.5 microg/kg or 0.25 microg/kg NFEP resulted in any significant changes in cardiorespiratory parameters, but plasma catecholamines increased (2- to 3-fold). Further studies are needed to determine the safety of NFEP that are specifically designed to assess the catecholamine response. Our results suggest that it is not advisable to initiate human PET studies with [18F]-NFEP without further evidence supporting its safety.
Molina
P E
PE
Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Ding
Y S
YS
Carroll
F I
FI
Liang
F
F
Volkow
N D
ND
Pappas
N
N
Kuhar
M
M
Abumrad
N
N
Gatley
S J
SJ
Fowler
J S
JS
D000818:Animals; D001549:Benzamides; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000633:toxicity*; D002245:Carbon Dioxide / Q000097:blood; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D005260:Female; D005462:Fluorine Radioisotopes; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood; D010215:Papio; D011725:Pyridines / Q000633:toxicity*; D019275:Radiopharmaceuticals / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005462:Fluorine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals; C115362:fluoronorchloroepibatidine; D002245:Carbon Dioxide; D010100:Oxygen; D009638:Norepinephrine; D004837:Epinephrine