The effect of intracerebroventricular D-ALA2 methionine enkephalinamide and naloxone on cardiovascular parameters in the cat.
Lathers and Schraeder (1) have shown that autonomic dysfunction is associated with epileptogenic activity induced by pentylenetetrazol while Vindrola et al (2) found increased D-ALA2 methionine-enkephalinamide (DAME) levels in the rat brain after pentylenetetrazol-induced epileptogenic activity. Thus, this study was designed to determine whether DAME could have contributed, at least in part, to the autonomic dysfunction associated with pentylenetetrazol-induced epileptogenic activity in the study of Lathers and Schraeder (1). DAME (500 micrograms/kg, icv) was given to 9 cats anesthetized with alpha chloralose. Epileptogenic activity and hypotension occurred in all cats (maximum fall ranging from 6 to 46 mmHg; duration of 6 to 35 min). In 6 cats the heart rate decreased, in 2 it increased, and in 1 it showed little or no change. The duration of heart rate changes varied from 18 to 76 min. Naloxone (100 micrograms/kg, iv) was given to 6 cats after DAME. Naloxone suppressed or abolished the epileptogenic activity in all 6 cats, reversed the DAME-induced hypotension and increased the heart rate in 3 cats, decreased it in 2, and produced no change in 1. These results indicate that DAME may produce epileptogenic activity and cardiovascular changes through an action on central opiate receptors. It is hypothesized that: 1) increased levels of DAME inhibit the release of gamma aminobutyric acid; 2) this then increases vagal bradycardia and hypotension; and 3) step 2 causes an imbalance in peripheral autonomic cardiac neural discharge which may cause arrhythmias and/or sudden unexplained death in the epileptic person.
Lathers
C M
CM
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia.
Tumer
N
N
Kraras
C M
CM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004827:Epilepsy / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008959:Models, Neurological; D009270:Naloxone / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D012016:Reference Values
D009270:Naloxone; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D010433:Pentylenetetrazole