PubMed Health⌕ Search

Biomedical subjects

G Anlezark

Publications and source records attributed to G Anlezark.

10 recordsLinked to original sources
PubMed1978

Blockade of photically induced epilepsy by 'dopamine agonist' ergot alkaloids.

The effect of the intravenous administration of ergot alkaloids on epileptic responses to intermittent photic stimulation )IPS) has been studied in adolescent baboons, Papio papio, from Senegal. Ergocornine, 1--2 mg/kg, produced marked autonomic and behavioural effects, slowed the EEG, and abolished myoclonic responses to IPS for 30--90 min. Ergometrine, 1 mg/kg, activated the EEG and blocked the induction of myoclonic responses for 1--3 h. Bromocriptine, 0.5--4 mg/kg, did not consistently prevent myoclonic responses to IPS. After pretreatment with a subconvulsant dose of allylglycine (180--200 mg/kg), lysergic acid diethylamide, 0.1 mg/kg, retained the capacity to block myoclonic responses to IPS, and ergocornine 1 mg/kg reduced such responses. The convulsant effect of allylglycine was enhanced, however, so that prolonged seizure sequences began 19--96 min after ergocornine administration. The protective action of ergot alkaloids against epileptic responses induced by sensory stimulation is interpreted in terms of effects at several sites, including dopaminergic and serotoninergic synapses.

Allyl Compounds↗
PubMed1977

Seizure activity in photosensitive baboons following antidepressant drugs and the role of serotoninergic mechanisms.

Laboratroy and clinical evidence indicates that tricyclic antidepressants lower seizure threshold and in high doses may induce generalised seizures. In baboons with photosensitive epilepsy (Papio papio) the effects of 2 tricyclic antidepressants (imipramine and chlorimipramine) and of maprotiline and Nomi fensine have been studied (i.v. dose range 1-20 mg/kg. Imipramine, chlorimipramine and maprotiline (10 mg/kg i.v.) lowered seizure threshold to a comparable extent, whereas Nomifensine (10 mg/kg i.v-) did not enhance myoclinic responses to photic stimulation. Generalised seizures were seen 15-30 min after imipramine or chlorimipramine (20 mg/kg), and these two drugs showed no difference in their epileptogenicity. Administration of 5-hydroxytryptophan (25 mg/kg i.v.) 90 min before chlorimipramine or imipramine (10 mg/kg) completely blocked the usual augmentation of photically-induced epileptic responses. It is concluded that enhancement of serotoninergic activity following blockade of 5-HT re-uptake within the brain is unlikely to be responsible for enhanced myoclonic responses and epileptogenic seizures seen after tricyclic antidepressants. Nomifensine is significantly less epileptogenic than imipramine or chlorimipramine.

5-Hydroxytryptophan↗
PubMed1977

Effect of nomifensine on brain amines and epilepsy in photosensitive baboons.

1. The literature, both clinical and experimental, suggests that tricyclic antidepressants are potentially epileptogenic. Using the experimental model of epilepsy provided by the photosensitive baboon, Papio papio, the epileptic potential of four antidepressant drugs, two of which are tricyclic, has been assessed. The drugs used were imipramine 1, 10 and 20 mg/kg, chlorimipramine 1, 10 and 20 mg/kg, maprotiline 1 and 10 mg/kg and nomifensine 10 and 20 mg/kg. In a second series of experiments the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) 10 and 25 mg/kg has been administered before administration of imipramine 10 mg/kg and chlorimipramine 10 mg/kg. 2. The results of the experiments indicate that at 10 mg/kg imipramine, chlorimipramine and maprotiline all induce seizures and lower the seizure threshold. In contrast nomifensine at this dose did not alter the seizure threshold. 5-HTP 25 mg/kg administered before the antidepressants, abolished seizures. These results are discussed in the light of other experiments which have attempted to explain the pathophysiology of epileptic seizures following antidepressants, and it is concluded that dopaminergic mechanisms are probably responsible for the differing effect noted with nomifensine.

Amines↗
PubMed1976

Ergot alkaloids as dopamine agonists: comparison in two rodent models.

A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protective effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic seizures was apomorphine greater than ergocornine greater than bromocryptine greater than ergometrine greater than LSD greater than methysergide greater than piribedil while that observed in the rotating mouse model was apomorphine greater than ergometrine greater than ergocornine greater than bromocryptine greater than piribedil. LSD caused only weak circling behaviour even when administered in high doses (greater than 1 mg/kg). Methysergide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed.

Acoustic Stimulation↗
PubMed1976

Inhibition of reflex epilepsy by (+/-)-N-n-propylnorapomorphine.

In baboons, Papio papio, spontaneously showing photosensitive epilepsy, myoclonic responses to intermittent photic stimulation were reduced or abolished for up to four hours by (+/-)-N-n-propylnorapomorphine (NPA) 0.05-0.2 mg/kg body weight, given i.v. In animals pretreated with allyglycine, 200 mg/kg, a transient abolition of myoclonic responses followed NPA, 0.2 mg/kg. In DBA/2 mice, seizures following auditory stimulation were attenuated or abolished by NPA 0.025-0.1 mg/kg given intraperitoneally (ED50 for abolition of clonic phase = 0.032 mg/kg). The ED50 for pentylenetetrazol seizures in MF 1 mice was not altered by NPA 0.25 mg/kg.

Animals↗
PubMed1975

Photically induced epilepsy in Papio papio as a model for drug studies.

Neurophysiological studies employing drugs have been undertaken in the natural syndrome of photically induced epilepsy in the Senegalese baboon Papio papio. GABA-mediated inhibition, both pre- and posysynaptic, plays an important role in the epileptic manifestations seen in this syndrome synapses can significantly modify photically induced epileptic responses, partly as a result of changes in afferent activity. The level of activity in dopaminergic systems can also modify the epileptic signs. Among anticonvulsant drugs, barbiturates and benzodiazepines are very effective against this type of epilepsy, whereas many other drugs are weakly active or toxic. A modification of the natural model (using allylglycine as a priming agent) is convenient for correlating acute anticonvulsant activity and neurological toxicity with plasma concentrations of anticonvulsant agents.

Acetylcholine↗
PubMedDate not supplied

Drugs modifying dopaminergic activity and behaviour, the EEG and epilepsy in Papio papio.

Acute changes in spontaneous motor activity, the EEG and photically induced epileptic responses have been observed in baboons (Papio papio) following the i.v. injection of drugs acting on dopaminergic transmission. Apomorphine hydrochloride, 0.5-1.0 mg/kg, produced a phase of acute excitement with accentuated vigilance and abnormal buccal motor activity lasting 30-40 min; during this phase myoclonic responses to intermittent photic stimulation were absent. After piribedil (ET 495, 1,2'' -pyrimidyl-4-piperonylpiperazine), 2-10 mg/kg, acute excitement was not seen. Intermittent delta activity was prominent in the EEG for 1-3 hr, and was associated with a slight reduction in photically induced epileptic responses. Haloperidol 0.6-1.2 mg/kg, produced a long-lasting reduction in spontaneous motor activity with an increased incidence of spontaneous EEG spikes and waves and a great enhancement of paroxysmal EEG activity during photic stimulation. Pimozide, 0.5-2.5 mg/kg, normally produced mild sedation and some EEG slowing. 2 animals responded idiosyncratically to both haloperidol and pimozide, displaying intermittent dystonic episodes with bucco-facial dyskinesia. These findings suggest that activation of dopaminergic receptors can lead to a reduction in myoclonic responses to photic stimulation.

Allyl Compounds↗