Treatment of tyramine-induced brain edema with anion transport inhibitor L-644,711.
Tyramine induces coma in phenelzine-treated dogs. Development of coma in these animals is associated with brain edema, abnormal brain scans of Tc-99m-diethylene-triamine-penta-acetic acid (Tc-99m-DTPA), and elevated levels of CSF catecholamines. We found that the intravenous administration of 6-7 mg/kg of a single dose of L-644,711 given fifteen minutes after the oral administration of tyramine to phenelzine-pretreated animals followed by an infusion of normal saline containing 6-7 mg/kg of the drug given over a period of 2 hr caused reversal of brain injury. This was accompanied by full recovery within a period of 24 hr of all the animals tested. A follow-up study revealed that 24 hr after treatment with L-644,711 CSF levels of catecholamines and brain images of Tc-99m-DTPA were indistinguishable from normal controls. Animals that received no drug died from unresolved coma within 4 to 24 hr. Animals that had recovered due to therapy with L-644,711 were given 10-14 days rest followed by a repetition of the phenelzine and tyramine treatment but denied L-644,711 therapy. These animals also died of unresolved coma within 24 hr. This preliminary study suggest that the use of L-644,711 may constitute an important advance in treatment of brain edema of a wide range of neurological disorders.
Faraj
B A
BA
Department of Radiology (Division of Nuclear Medicine), Emory University School of Medicine, Atlanta, Georgia 30322.
Cragoe
E J
EJ
Sarper
R
R
Camp
M
M
Malveaux
E
E
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D001929:Brain Edema / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D003128:Coma; D004232:Diuretics; D004298:Dopamine / Q000134:cerebrospinal fluid; D004837:Epinephrine / Q000134:cerebrospinal fluid; D005449:Fluorenes / Q000627:therapeutic use*; D008297:Male; D009638:Norepinephrine / Q000134:cerebrospinal fluid; D009942:Organometallic Compounds; D004369:Pentetic Acid; D010624:Phenelzine / Q000494:pharmacology; D011877:Radionuclide Imaging; D051381:Rats; D016284:Technetium Tc 99m Pentetate; D014439:Tyramine
D004232:Diuretics; D005449:Fluorenes; D009942:Organometallic Compounds; D004369:Pentetic Acid; D010624:Phenelzine; C053396:L 644711; D004298:Dopamine; D016284:Technetium Tc 99m Pentetate; D009638:Norepinephrine; D014439:Tyramine; D004837:Epinephrine