The toxicity and mutagenicity of S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (IBZM), a new CNS D-2 dopamine receptor imaging agent.
IBZM is one of several benzamide derivatives showing a high affinity for the CNS D-2 dopamine receptor. Carrier-free [123I]IBZM is potentially useful as a nuclear medicine imaging agent for investigating CNS D-2 dopamine receptor in humans. This study describes the acute toxicity of IBZM in the rat and rabbit, its subchronic toxicity in the rabbit and its mutagenicity measured by the Ames test. IBZM had a 24 hour LD50 of 400 mg/kg in the rat and 50 mg/kg in the rabbit when administered i.v. Deaths occurred within minutes of dosing. Some necrosis was evident at the injection site in IBZM treated animals which was not found in the controls. No gross or histological differences between experimental animals and controls were evident in surviving animals when necropsied 14 days after dosing. Repeated exposure of rabbits to IBZM at a total cumulative dose of 100,000 times the expected clinical dose revealed no consistent changes in hematology, blood chemistry, blood enzymes or tissue pathology. IBZM was not mutagenic in the modified Ames assay with or without metabolic activation in the TA98 and TA100 tester strains. It is therefore unlikely that acute adverse effects will be associated with the diagnostic use of this drug in man.
Kostyniak
P J
PJ
Department of Pharmacology and Therapeutics, State University of New York, Buffalo 14214.
Brenner
J S
JS
Maccubbin
A E
AE
Nakeeb
S
S
Kasliwal
R
R
Kung
H F
HF
D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2; D012486:Salmonella typhimurium / Q000235:genetics
D001549:Benzamides; D009153:Mutagens; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide