d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Seizures

FK-33,824 (Tyr-D-Ala-Gly-MePhe-Met(O)-ol) and metkephamid (Tyr-D-Ala-Gly-Phe-N(Me)Met-CONH2; LY 127623) are two parenterally active synthetic analogues of the endogenous morphinomimetic pentapeptide, [Met5]-enkephalin. Acute s.c. administration of each analogue raised the seizure threshold in a dose-related manner in rats challenged with flurothyl, a volatile convulsant. The anticonvulsant action was antagonized by a low dose of naloxone (0.10 mg/kg s.c.). FK-33,824 and metkephamid can therefore be classified with typical mu-receptor agonists such as morphine and etorphine in this procedure.

Topics: Animals; Anticonvulsants; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dose-Response Relationship, Drug; Endorphins; Enkephalin, Methionine; Enkephalins; Flurothyl; Male; Naloxone; Rats; Seizures

Baboons (Papio papio) with photosensitive have been chronically prepared with guide cannulae and deep electrodes to study the effects of focal injections of opioids. In the hippocampus, amygdala and thalamus (centre median) 50--100 micrograms morphine, 20--100 micrograms Met-enkephalin or 2--10 micrograms FK 33,824 do not induce local or general electrographic or motor signs of epilepsy. The acute epileptogenic effect of morphine and enkephalins observed in rats is not a general phenomenon whereas the anticonvulsant action of opioids acting on mu-receptors is seen in rodents and primates.

Topics: Amygdala; Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Electroencephalography; Enkephalin, Methionine; Enkephalins; Hippocampus; Injections, Intraventricular; Light; Morphine; Narcotics; Papio; Seizures; Thalamus

Topics: Animals; Behavior, Animal; Cerebral Ventricles; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dose-Response Relationship, Drug; Electroencephalography; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Female; Injections, Intraventricular; Male; Morphine; Nalorphine; Rabbits; Rats; Seizures