dihydroergotoxine and Seizures

alpha-Dihydroergocryptine (alpha-DHEC) is a well known dopaminergic agent successfully employed in the treatment of Parkinson's disease. alpha-DHEC showed a neuroprotective activity against total cerebral ischemia induced by MgCl2 in mice and histocytic anoxia by NaCN in mice and rats. Moreover the drug promoted the recovery of locomotor activity in rats after cerebral ischemic damage and protected mice against convulsions induced by intracerebroventricular injections of NMDA and glutamate. alpha-DHEC showed a protective activity on neuronal degeneration induced by MPTP in monkeys, as evaluated through animal's behaviour and morphological-cytochemical changes in the substantia nigra, suggesting a preservative effect on neuronal morphology and brain architecture. In the MPTP-treated monkeys, the alpha-DHEC administration induced a restoration of the unstimulated MDA values to control levels. The neuroprotective activity of alpha-DHEC is related to its peculiar activity on antioxidative enzymes of GSH system and to reduction of lipid-peroxide-induced cellular degeneration.

Topics: Animals; Brain Ischemia; Constriction; Dihydroergotoxine; Disease Models, Animal; Hypoxia, Brain; Injections, Intraventricular; Macaca fascicularis; Male; Mice; Mice, Inbred ICR; Motor Activity; Neuroprotective Agents; Parkinson Disease, Secondary; Rats; Seizures

The influence of several nootropic drugs (piracetam, pyritinol, meclofenoxat, methylglucamine orotate (MGO) and dihydroergotoxine (DHET) on both the ethanol preference and the enhanced seizure susceptibility after a single dose of ethanol was studied. Piracetam, MGO and DHET reduce the ethanol drinking in ethanol-preferring mice. The enhanced seizure susceptibility after a single dose of ethanol was abolished by piracetam and MGO.

Topics: Alcohol Drinking; Alcoholism; Animals; Dihydroergotoxine; Ethanol; Male; Meglumine; Mice; Mice, Inbred ICR; Orotic Acid; Piracetam; Seizures; Substance Withdrawal Syndrome; Synapses; Trapidil

The study was undertaken to test further whether diminished GABAergic transmission might be responsible for the increased susceptibility of rats to picrotoxin-induced convulsions. In rats kept individually in cages in a noise-free room, the time between the intraperitoneal injection of the convulsant agent and the onset of convulsions was measured. Acute and subacute treatment with low doses of dihydroergotoxine (0.01-1.0 mg/kg) increased the occurrence and decreased the latency of picrotoxin-induced convulsions. Acute administration of dihydroergotoxine, 1.0 mg/kg, caused convulsions in animals injected with the subconvulsive dose (3 mg/kg) of bicuculline and of 10.0 mg/kg dihydroergotoxine in animals injected with the subconvulsive dose (1.5 mg/kg) of strychnine. Some of the animals injected with the 100% convulsive dose of strychnine were protected by dihydroergotoxine pretreatment (1.0 mg/kg) as evidenced by the lower occurrence of convulsions and fewer animals dying, as well as by a delay in the appearance of convulsions at 10.0 mg/kg. These results together with the previous findings on the GABA system suggest that dihydroergotoxine potentiates the appearance of picrotoxin and bicuculline-induced convulsions by a diminution of GABAergic transmission.

Topics: Animals; Bicuculline; Convulsants; Dihydroergotoxine; Drug Synergism; gamma-Aminobutyric Acid; Male; Picrotoxin; Rats; Rats, Inbred Strains; Seizures; Strychnine

Dihydroergotoxine administration shortened the latency of allylglycine-and picrotoxin-induced convulsions in rats and increased the incidence of convulsions elicited by picrotoxin, i.e., it lowered ED50 for picrotoxin. The same drug (0.1-10.0 mg/kg) decreased the levels of gamma-aminobutyric acid (GABA) in the caudate nucleus and cingulate cortex, but enhanced the aminooxyacetic acid induced accumulation of GABA indicating an increased synthesis of GABA in these brain regions. The concentrations of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine in the whole rate brain were not affected with doses of dihydroergotoxine up to 10.0 mg/kg, but this dose of the drug slowed down the turnover of dopamine, as evidenced by a diminished disappearance of dopamine induced by alpha-methyl-p-tyrosine administration. The results suggest that dihydroergotoxine decreases GABA-ergic transmission and, therefore, presumably lowers the seizure threshold.

Topics: Allylglycine; Animals; Brain Chemistry; Catecholamines; Dihydroergotoxine; Drug Interactions; gamma-Aminobutyric Acid; Male; Picrotoxin; Rats; Rats, Inbred Strains; Seizures

Harmaline and ibogaine i.v. administration induced in the photosensitive baboon restlesness and tremor (8-12 Hz). The former increased the EEG frequency particularly in central regions with appearance of bursts at 20-24 c/s and blocked by somatic movement. The latter produced a slight enhancement of frontal fast rhythms. Both drugs blocked the spontaneous paroxysmal activity with little effect on photosensitivity. These effects lasted for 2-4 hrs. Vincamine produced agitation during 15 min. post-i.v.-administration and showed an "hypervigilant" EEG. Nor vincamine or Hydergine altered the degree of photosensitivity. Cerebellar involvement in the action of harmaline and ibogaïne is discussed.

Topics: Alkaloids; Animals; Cerebral Cortex; Dihydroergotoxine; Haplorhini; Harmaline; Ibogaine; Papio; Photosensitivity Disorders; Seizures; Tremor; Vinca Alkaloids

Topics: Acetylcholine; Animals; Atropine; Chlorpromazine; Dihydroergotoxine; Drug Interactions; Electroencephalography; Epinephrine; Hippocampus; Hydrocortisone; Hypothalamus; Limbic System; Mesencephalon; Norepinephrine; Rabbits; Rats; Receptors, Adrenergic; Reticular Formation; Seizures; Serotonin; Stimulation, Chemical