Anticonvulsant and antiarrhythmic actions of the beta blocking agent timolol.
Cats were anesthetized with alpha-chloralose and pentylenetetrazol, 10 and/or 20 mg were administered intracerebroventricularly (i.c.v.) to elicit epileptiform activity, including both interictal and ictal discharges. Timolol, 10, 100, 500 micrograms/kg i.c.v. and 1, 5, 10 and/or 20 mg/kg i.v., was administered at 5 min intervals to determine whether it suppressed the epileptiform activity. Mean arterial blood pressure and heart rate increased after the administration of pentylenetetrazol; these increases were associated with the development of epileptiform activity and cardiac arrhythmias. All doses of timolol caused a decrease in the blood pressure and heart rate elevated by pentylenetetrazol and suppressed the epileptiform activity. Similar findings were obtained in cats that received the same doses of timolol administered at different time intervals. The data indicate that the central administration of timolol reverses the epileptiform activity of pentylenetetrazol in the brain and suppresses the associated increases in blood pressure, heart rate and cardiac arrhythmias.
Lathers
C M
CM
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Stauffer
A Z
AZ
Tumer
N
N
Kraras
C M
CM
Goldman
B D
BD
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013999:Timolol / Q000008:administration & dosage / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D013999:Timolol; D010433:Pentylenetetrazole