Dimaprit--induced neurotoxicity.
The neurotoxicity of the histamine H2 agonist dimaprit was characterized. Dimaprit (100 micrograms administered into the lateral cerebral ventricle) induced a large area of brain necrosis 1-3 days later which was uniformly lethal. Lower doses caused dose - related effects on survival, gross brain pathology and body weight. Experiments with other H2 agonists and H2 antagonists, together with studies by others demonstrating a similar toxicity of the congener homodimaprit suggest that the neurotoxicity of dimaprit is independent of brain H2 receptors. Although dimaprit is a useful tool for the characterization of H2 receptor responses, the present results show that this agent must be used with caution, if at all, in classifying brain H2-receptor mediated events.
Swaab
R L
RL
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Battles
A M
AM
Bruner
C A
CA
Hough
L B
LB
D000818:Animals; D017259:Dimaprit; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013890:Thiourea / Q000008:administration & dosage / Q000633:toxicity*
D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D013890:Thiourea; D017259:Dimaprit