ergoline and Seizures

Mycotoxins are fungal metabolites that induce undesirable effects. The effects of these mycotoxins vary depending on the chemical structure of the toxin and degree of toxicity. Mycotoxins that induce muscle tremors, ataxia, and convulsions are termed tremorgenic mycotoxins. Our report documents the clinical course of 4 dogs from a single household that were simultaneously affected by tremorgenic mycotoxins. Diagnosis of tremorgenic mycotoxicosis was confirmed by stomach content analysis from 1 of the dogs. The mycotoxins identified were penitrem A and roquefortine, which are both produced by Penicillium spp. Treatment goals following tremorgenic mycotoxin ingestion include minimizing absorption, controlling tremors and seizures with methocarbamol and pentobarbital sodium administration, and providing supportive care. Two of the affected dogs required ventilatory support. With early aggressive treatment, prognosis is good and recovery is complete without sequelae. It is helpful for the clinician to be familiar with the typical clinical signs at the time of admission, treatment, and clinical course of dogs with tremorgenic mycotoxicosis.

Topics: Animals; Ataxia; Dog Diseases; Dogs; Ergolines; Gastrointestinal Contents; Heterocyclic Compounds, 4 or More Rings; Indoles; Male; Mycotoxicosis; Mycotoxins; Piperazines; Seizures; Tremor

Penitrem A and roquefortine poisonings were diagnosed in a Laborador retriever following garbage consumption. Clinical signs of mycotoxicosis included polypnea, tachycardia, and ataxia that quickly progressed to lateral recumbency and seizures. Removal of the mycotoxins from the stomach soon after ingestion allowed the dog to recover within 72-96 hours.

Topics: Animals; Ataxia; Dog Diseases; Dogs; Ergolines; Heterocyclic Compounds, 4 or More Rings; Indoles; Male; Mycotoxicosis; Mycotoxins; Piperazines; Seizures

Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including 5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken to determine whether antagonism of the newly identified 5-HT7 receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their affinity at the 5-HT7 receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT7 receptor and a statistically significant correlation was observed between 5-HT7 affinity and doses for half-maximal response (ED50) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT1A, 5-HT2A or 5-HT2C receptors. It is also unlikely that interactions between the 5-ht5 receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this in vivo model have no affinity for the 5-ht5 receptor. There are similarities between the pharmacology of the 5-HT7 receptor and that of the 5-HT1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT1A affinity was not significant. Furthermore, the 5-HT1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT7 receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with selective 5-HT7 antagonists.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; CHO Cells; Cricetinae; Ergolines; Male; Methysergide; Mianserin; Mice; Mice, Inbred DBA; Receptors, Serotonin; Seizures; Serotonin Antagonists

The discrete localization of D3 receptors in the nucleus accumbens and subjacent islands of Calleja bears a close resemblance to the dopamine-sensitive anticonvulsant site in the anteroventral striatum. To determine if these D3 receptors were capable of attenuating limbic motor seizures induced by pilocarpine, dopamine agonists with preferential or non-selective D3 affinity were injected stereotaxically into these limbic brain regions of the rat via indwelling cannulae prior to pilocarpine challenge. Reliable clonic seizures were obtained by administering the proconvulsive dopamine D1 agonist SKF 38393 (10 mg/kg i.p.) followed by a subconvulsant dose of pilocarpine (280-300 mg/kg i.p.). Bilateral intra-accumbens pretreatment with the D3 > D2 agonist RU 24213 (0.2 pmol-7 nmol) significantly delayed the onset of seizures, with a minimum effective dose of 2 pmol, without altering their frequency or severity. The more selective D3 agonist LY 171555 (0.2 pmol-7.8 nmol) was less potent, and only attenuated pilocarpine-induced seizures at a dose (500 pmol) that would have stimulated accumbens D2 receptors as well. Intra-accumbens injections of the highly potent and selective D3 agonist 7-OH-DPAT (20 pmol to 7 nmol) afforded no protection against pilocarpine-induced seizures. Apomorphine, a mixed D1/D2/D3 agonist, delayed seizure onset at 100-500 pmol, but not at higher doses. RU 24213, LY 171555 and 7-OH-DPAT were all modestly anticonvulsant when microinjected into the islands of Calleja at D2/D3 unselective doses. These data support the notion that dopamine systems limit seizure propagation through the limbic forebrain, but suggest this protective effect is mediated by D2 rather than D3 receptors.

Topics: Animals; Apomorphine; Dopamine Agents; Ergolines; Injections; Limbic System; Male; Nucleus Accumbens; Olfactory Bulb; Phenethylamines; Pilocarpine; Quinpirole; Rats; Rats, Wistar; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Seizures

This study examined the role of hippocampal dopamine D2 receptors in the genesis of limbic seizures induced by muscarinic agonists in the rat. Pilocarpine, 600 mg/kg, elicited rapid and usually fatal convulsions. These were not affected by focal injections of saline (1 microliter) into both hippocampi. Pretreatment of the dorsal, but not the lateral hippocampus, with the D2 agonist trans-(+)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo-(3,4-g)quinol ine hydrochloride (LY 171555, 2 micrograms per side), did not alter the frequency of pilocarpine-induced convulsions, but significantly delayed their appearance and reduced their intensity. LY 171555 similarly increased the latency of seizures induced by focal hippocampal injection of carbachol (100 micrograms), without changing the frequency or the severity. The selective D2 antagonist raclopride, injected dorsally into both hippocampi dose-dependently facilitated motor seizures evoked by pilocarpine (100 mg/kg), the cholinomimetic at this dose being ineffective as a convulsant in saline-treated animals. Intrahippocampal administration of the D1 agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 2 micrograms per side) did not facilitate pilocarpine seizures and did not potentiate the proconvulsant action of raclopride. These data demonstrate that activation of the dopaminergic system, via D2 receptors in the dorsal hippocampus, is capable of protecting the animal against limbic motor seizures arising from excessive muscarinic stimulation of the hippocampus. Since the blockade of D2 receptors in the hippocampus markedly lowered the seizure threshold to pilocarpine, this would suggest that the dopaminergic input to the hippocampus is normally tonically active and functions physiologically to prevent epileptogenesis.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Dopamine; Dopamine Agents; Dopamine D2 Receptor Antagonists; Ergolines; Female; Hippocampus; Injections; Male; Pilocarpine; Quinpirole; Raclopride; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D2; Salicylamides; Seizures; Stereotaxic Techniques

The effects of the new 5HT1A receptor antagonist (S)-UH-301 were investigated in several neurological and behavioral tests in rodents and monkeys. By itself, (S)-UH-301 was found to decrease palatable food consumption in rats, to exhibit anticonvulsant activity in mice, and anxiolytic-like properties in two rodent models of anxiety (light-dark test and elevated plus-maze test). (S)-UH-301 antagonized various symptoms and behaviors induced by the selective 5HT1A receptor agonist 8-OH-DPAT, such as lower lip retraction and flat body posture in rats, hyperphagia for palatable food in rats, and displacement activities (considered as indices of anxiety) in squirrel monkeys. These results further characterize (S)-UH-301 as an in vivo active 5HT1A receptor antagonist and suggest that this antagonistic activity might confer the compound with anxiolytic-like properties.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Acoustic Stimulation; Animals; Brain; Cerebral Ventricles; Conditioning, Operant; Conflict, Psychological; Ergolines; Exploratory Behavior; Feeding Behavior; Injections, Intraventricular; Ketanserin; Learning; Mice; Mice, Inbred DBA; Motor Activity; N-Methylaspartate; Rats; Receptors, Serotonin; Seizures; Serotonin; Serotonin Antagonists

In the pilocarpine model of epilepsy, dopamine can either inhibit (via D2 receptors) or facilitate (via D1 receptors) the spread of limbic motor seizures. The anticonvulsant action of D2 receptor activation has been localized to the anterior striatum, but disappears if excessive damage is caused to the overlying cerebral cortex. This study examines the possibility that the corticostriatal projection is involved in the anticonvulsant response to striatal D2 receptor stimulation, by comparing the seizure-protecting efficacy of intrastriatal trans-(+)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo-(3,4-g)quinol ine hydrochloride (LY 171555) in control rats, and in rats bearing discrete bilateral kainic acid lesions of the cerebral cortex. The results show that neurotoxin injection induces a punctate lesion of the primary motor area of the cortex in each hemisphere, with no injury to the underlying caudate-putamen, or to more distant structures such as the hippocampus. The lesion, however, was sufficient to abolish the protective effect of intrastriatal LY 171555 against pilocarpine challenge. To explain these findings, an interplay between nigrostriatal dopaminergic and corticostriatal glutamatergic neurons is proposed, in which the anticonvulsant tendency of the excitatory amino acid is accentuated by dopamine, probably by acting on D2 receptors which facilitate the release of glutamate from axon terminals.

Topics: Animals; Anticonvulsants; Cerebral Cortex; Corpus Striatum; Dopamine Agents; Ergolines; Female; Kainic Acid; Male; Motor Cortex; Pilocarpine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D2; Seizures; Stereotaxic Techniques

Recent radioligand binding studies demonstrated an increase in the density of dopamine D2 receptors in the nucleus accumbens ipsilateral to the stimulating electrode in amygdala- or hippocampal-kindled rats. In the present study we examined the anticonvulsant effect of dopamine agonists by unilateral microinjections into the nucleus accumbens in rats kindled from the right basolateral amygdaloid nucleus. Microinjections of the D2 agonist LY 171555 into the ipsilateral nucleus accumbens 15 min prior to the kindling stimulation in fully kindled rats decreased significantly kindling parameters such as seizure severity, seizure duration and afterdischarge duration, whereas the D1 agonist SKF 38393 had no anticonvulsant effects. After ipsilateral microinjection of 40 pmol LY 171555 focal and generalized kindled seizures were totally blocked in almost 50% of the rats. The anticonvulsant effect of LY 171555 could be completely antagonised by systemic administration of the D2 antagonist sulpiride. Microinjection of the D1 or D2 agonist into the nucleus accumbens contralateral to the stimulating electrode had no anticonvulsant effects. In accordance with other reports our data indicate a possible topographic limitation of D2 receptor mediated anticonvulsant effects to specific regions of the basal ganglia.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amygdala; Animals; Anticonvulsants; Dopamine Agents; Electric Stimulation; Ergolines; Female; Functional Laterality; Kindling, Neurologic; Microinjections; Nucleus Accumbens; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D2; Seizures; Sulpiride

This study employed the pilocarpine model of epilepsy to determine the relative systemic anticonvulsant potencies of five different D-2 agonists in the mouse, and to investigate the site of anticonvulsant action of LY 171555 in the rat's brain following intracerebral microinjection. Control mice pretreated with saline developed motor seizures when challenged with pilocarpine (400 mg/kg, 11/13 convulsed). D-2 agonists protected mice against pilocarpine-induced seizures in the rank order of potency PHNO greater than pergolide greater than greater than lisuride = LY 171555 much greater than RU 24213, with ED50 values ranging from 0.17 mg/kg for PHNO to greater than 4.5 mg/kg for RU 24213. The response to LY 171555 was abolished by the D-2 blocker metoclopramide (1.25 mg/kg), but not by the D-1 antagonist SCH 23390 (0.25 mg/kg). All D-2 agonists induced head-down sniffing and forward locomotion, consistent with central D-2 activation. LY 171555 (ED50 0.19 mg/kg), but not RU 24213 (ED50 greater than 4.5 mg/kg), was similarly efficacious in the rat. When injected into both hemispheres of the conscious rat via indwelling cannulae, intrastriatal saline failed to afford protection against the convulsant action of pilocarpine (600 mg/kg, 13/15 convulsed), whereas LY 171555 did (1 microgram, 1/12 convulsed). Intrastriatal RU 24213 (1 microgram per side) was without effect (7/10 convulsed). Similarly, no protection resulted when saline (15/16 convulsed) or LY 171555 (1 microgram, 17/23 convulsed) were delivered into both nigras. It is concluded that in this model of limbic seizures in the mouse and rat, D-2 agonists exert a powerful anticonvulsant effect which is mediated by D-2 receptors in the striatum, but not by D-2 receptors in the substantia nigra.

Topics: Animals; Corpus Striatum; Ergolines; Female; Male; Mice; Microinjections; Pilocarpine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Seizures; Substantia Nigra

Mice injected with pilocarpine (100-400 mg/kg plus 1 mg/kg methylscopolamine), picrotoxin (0.75-6 mg/kg) or strychnine (0.75-6 mg/kg) exhibited clonic or clonic/tonic convulsions. Pretreatment with the D-1 agonist CY 208-243 (0.375-1.5 mg/kg) dose-dependently potentiated the convulsions elicited by 100 mg/kg pilocarpine, but had neither a convulsant nor anticonvulsant effect in mice receiving picrotoxin (3 or 6 mg/kg) or strychnine (0.75 or 1.5 mg/kg). This facilitatory effect of CY 208-243 was abolished by the D-1 antagonist SCH 23390 (0.2 mg/kg). SCH 23390 by itself (0.05-0.8 mg/kg) dose-dependently protected mice against pilocarpine (400 mg/kg) seizures. Stimulating D-2 receptors with LY 171555 (0.167-4.5 mg/kg) dose-dependently protected mice against seizure activity induced by pilocarpine, but neither protected nor sensitised mice given picrotoxin or strychnine. The neuroleptics haloperidol (1-4 mg/kg), sulpiride (10-50 mg/kg), metoclopramide (1.25-6.25 mg/kg), thioridazine (0.5-2 mg/kg) and clozapine (0.5-2 mg/kg) had no effect on the seizure threshold to 100 mg/kg pilocarpine by themselves, although 10 mg/kg thioridazine and clozapine caused 100% convulsions, possibly through a toxic action. When administered in conjunction with a minimally effective quantity of CY 208-243 (0.375 mg/kg), however, all five neuroleptics interacted synergistically with the D-1 agonist to promote convulsions to pilocarpine (100 mg/kg). No such interaction occurred between submaximally protective doses of the D-1 blocker SCH 23390 (0.05 and 0.2 mg/kg) and a wide range of doses of the D-2 stimulant LY 171555 (0.167-4.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antipsychotic Agents; Apomorphine; Benzazepines; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Drug Synergism; Ergolines; Female; Indoles; Male; Mice; Phenanthridines; Picrotoxin; Pilocarpine; Quinpirole; Seizures; Strychnine

This study investigates the role of forebrain D1 receptors in the motor expression of seizures induced by pilocarpine. Conscious rats receiving bilateral intracaudate injections of saline, just failed to convulse to 200 mg/kg pilocarpine, but responded vigorously to 600 mg/kg of the cholinomimetic. LY 171555 significantly protected rats against 600 mg/kg pilocarpine, when delivered into the anterior striatum, as also did SCH 23390, from all rostrocaudal levels of the striatum. Intrastriatal SKF 38393 or CY 208-243 neither facilitated nor ameliorated pilocarpine-induced convulsions. SCH 23390 was also anticonvulsant from the nucleus accumbens, while intra-accumbens CY 208-243 was without effect. It is concluded that SCH 23390 affords protection against pilocarpine-induced limbic motor seizures by blocking the effects of endogenous dopamine released tonically onto D1 receptors in the corpus striatum and nucleus accumbens. The inability of additional D1 receptor stimulation to intensify such seizures, could indicate that forebrain D1 receptors are already maximally stimulated by the endogenous transmitter.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Anticonvulsants; Antiparkinson Agents; Benzazepines; Corpus Striatum; Dopamine Agents; Ergolines; Female; Indoles; Injections; Male; Nucleus Accumbens; Phenanthridines; Pilocarpine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Seizures; Stereotaxic Techniques

The involvement of dopamine (DA) in human and experimental epilepsy has been discounted as DAergic drugs have little effect on convulsions. This work presents evidence that bilateral microinjection of the DAD1 agonist SKF-38393 into the substantia nigra enhances the susceptibility of rats to seizures, with an ED50 of 20 pmol (range 13-31 pmol), converting subconvulsant doses of the cholinergic agonist pilocarpine (200 mg/kg; i.p.) into convulsant ones. The proconvulsant action of SKF-38393 was reversed by blocking D1-mediated transmission in the substantia nigra with the D1 antagonist SCH-23390. The D2 agonist LY-171555 did not modulate the threshold for limbic seizures when injected into the substantia nigra. In the striatum, the D2 agonist LY-171555 protected rats against limbic seizures induced by systemic administration of pilocarpine (380 mg/kg; i.p.), with an ED50 of 2 pmol (range 1.4-2.8 pmol). The anticonvulsant action of LY-171555 in the striatum was reversed by haloperidol. The D1 agonist SKF-38393 did not affect pilocarpine seizures following administration into the striatum. Systemic administration of DAergic drugs showed that the D1 agonist SKF-38393 decreased the threshold for pilocarpine seizures, with an ED50 of 0.81 mg/kg (range 0.45-1.47 mg/kg), whereas the D2 agonist LY-171555 had no effect on susceptibility of rats to pilocarpine. The proconvulsant action of SKF-38393 was blocked by the D1 antagonist SCH-23390. These results suggest that DA differentially modulates seizure threshold in the forebrain acting via D1 mechanisms in the substantia nigra and D2 mechanisms in the striatum.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Ergolines; Male; Pilocarpine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D1; Seizures; Substantia Nigra

The contribution of dopaminergic mechanisms to the generalization of epileptic activity was studied in rats given pilocarpine after pretreatment with selective dopamine agonists. At the dose of 200 mg/kg, pilocarpine produced limbic stereotypes but not convulsions or seizure-related brain damage. Pilocarpine, 200 mg/kg, following pretreatment with the D1 agonist (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3 benzazepine, but not its (S)-enantiomer, induced convulsive activity as revealed by behavioral, electroencephalographic alterations and widespread brain damage. These features were identical to those produced by a higher, convulsant dose of pilocarpine (400 mg/kg). On the other hand, pretreatment with the D2 agonist 4,4a,5,6,7,8,8a,9-octahydro-5-n-propyl-2H-pyrazolo-3,4-g-quinoline failed to induce convulsions. Furthermore, the D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-n-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine -7-ol prevented the convulsive activity induced by both 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3 benzazepine plus pilocarpine (200 mg/kg) and pilocarpine (400 mg/kg), given alone. However, neither dopamine agonists nor antagonists altered the limbic stereotypes induced by pilocarpine, suggesting a dopamine system involvement primarily in the mechanisms of epilepsy generalization. The results suggest that pharmacological manipulation of dopaminergic transmission may provide an alternative approach to therapy of secondarily generalized epilepsy.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Dose-Response Relationship, Drug; Ergolines; Male; Pilocarpine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D1; Seizures

Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypies but neither convulsions nor seizure-related brain damage. The pretreatment, 5 minutes prior pilocarpine, with the D-1 agonist SKF 38393 (-ED50 = 1 mg/kg; i.p.) induced convulsions similar to those produced by a higher, convulsant dose of pilocarpine. On the other hand, the pretreatment with the D-2 agonist LY 171555 failed to induce convulsions. The D-1 receptor antagonist SCH 23390 prevented the convulsions induced by SKF 38393 plus pilocarpine (200 mg/kg). This study indicates that D-1, but not D-2, receptor stimulation converts subconvulsant doses of pilocarpine into convulsant ones.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Convulsants; Dopamine Agents; Drug Synergism; Ergolines; Male; Pilocarpine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Seizures

Two ergot derivatives, lisuride and quinpirole, were examined for their ability to antagonize hyperbaric oxygen-induced (5 ATA O2) convulsions in mice. Significant protection was obtained by lisuride (25-400 micrograms.kg-1, i.p.) and quinpirole (100-200 micrograms.kg-1, i.p.). The efficacy was found to be about 50% of the protection obtained by diazepam (4 mg.kg-1, i.p.). Both lisuride and quinpirole significantly reduced rectal temperature at all doses administered. In separate experiments, at normal atmospheric conditions, all drugs to some extent reduced estimated respiratory minute volume. Taking these effects into account, lisuride is considerably more active as an anticonvulsant than quinpirole.

Topics: Animals; Body Temperature; Diazepam; Dopamine Agents; Drug Interactions; Ergolines; Haloperidol; Hyperbaric Oxygenation; Lisuride; Lung Volume Measurements; Male; Mice; Mice, Inbred CBA; Quinpirole; Seizures

Effects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline (16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80-83% in the control to 50-55%). In gerbils, nicergoline (32 mg/kg, i.p.) significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20-100 microM) on LPOF is more potent than those of alpha-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.

Topics: Animals; Brain; Brain Ischemia; Dihydroergotamine; Energy Metabolism; Ergolines; Female; Gerbillinae; Lipid Peroxides; Male; Mice; Mice, Inbred ICR; Nicergoline; Rats; Rats, Inbred Strains; Seizures

Pharmacological investigations of the ergot alkaloid of the group of clavines, elymoclavine, isolated from Claviceps sp. cp. II showed the following results: The LD50 for mice for 24 h was 350 (228-535) mg/kg and for rats 145 (81-258) mg/kg. Elymoclavine induced a dose-dependent stereotypy (doses of 2 to 10 mg/kg) in rats and mice which was antagonized by haloperidol and pimozide. It prevented the development of haloperidol catalepsy in rats and produced rotations contralateral to the striatal lesions with 6-OHDA which were antagonized by pimozide and partly by cyproheptadine. Elymoclavine, like bromocriptine, decreased the plasma level of prolactin. Furthermore, elymoclavine increased the exploratory activity of rats in open field; this effect was antagonized by haloperidol and was essentially influenced by many substances acting on different transmitter systems (NA, DA, GABA). Elymoclavine inhibited the picrotoxin and electroshock convulsive seizures but potentiated the pentylenetetrazol ones in mice as these effects were differently influenced by pimozide, haloperidol, 5-HTP, atropine and phentolamine. 100 and 250 micrograms/kg of elymoclavine produced a considerable and persisting decrease of the blood pressure in anaesthetized cats. At 1 X 10(-6) M, without producing any per se effect, elyoclavine decreased the contractile effects of acetylcholine, nicotine, BaCl2 and PGE1 as well as the field electrical stimulation-induced contractions in an isolated segment from guinea-pig ileum. The observed effects of elymoclavine are mainly due to its dopaminergic agonist action. It seems, however, that influences on other transmitter receptors also underlie the mechanism of action of this ergot alkaloid.

Topics: Animals; Behavior, Animal; Blood Pressure; Catalepsy; Corpus Striatum; Ergolines; Exploratory Behavior; Guinea Pigs; Humans; Hydroxydopamines; Ileum; Lethal Dose 50; Mice; Muscle Contraction; Muscle, Smooth; Oxidopamine; Prolactin; Rats; Seizures; Stereotyped Behavior

The pharmacological investigation of the ergot alkaloid of the group of clavines elymoclavine isolated from Claviceps sp. cp. II showed the following: LD50 for mice for 24 hours was 350 (228 divided by 535) mg/kg and for rats--145 (81 divided by 258) mg/kg; elymoclavine induced a dose-dependent stereotypy in rats and mice which was antagonized by haloperidol and pimozide; it prevented the development of haloperidol catalepsy in rats and produced rotations contralateral to the striatal lesions with 6-OHDA which were antagonized by pimozide and partly by cyproheptadine. Elymoclavine increased the exploratory activity of rats in open field as this effect was antagonized by haloperidol and was essentially influenced by many substances acting on different transmitter systems (NA, DA, GABA). Elymoclavine inhibited the picroroxin and electroshock convulsive seizures but potentiated the pentylenetetrazol ones in mice as these effects were differently influenced by pimozide, haloperidol, 5-HT, atropine and phentolamine. The observed effects of elymoclavine are mainly due to its DAergic agonistic action. It seems, however, that influences on other transmitter receptors also underlie the mechanism of action of this ergot alkaloid.

Topics: Animals; Bromocriptine; Catalepsy; Central Nervous System; Corpus Striatum; Ergolines; Exploratory Behavior; Haloperidol; Humans; Hydroxydopamines; Mice; Oxidopamine; Pimozide; Rats; Receptors, Dopamine; Seizures; Stereotyped Behavior; Sympathetic Nervous System

Topics: Acoustic Stimulation; Animals; Apomorphine; Biogenic Amines; Brain; Bromocriptine; Dopamine; Ergolines; Ergonovine; Female; Lysergic Acid Diethylamide; Male; Mice; Mice, Inbred DBA; Quipazine; Seizures

Audiogenic seizures in DBA/2 mice have been studied after administration of drugs believed to act as dopamine agonists. Apomorphine at 0.4 mg/kg delays all phases of the response, the tonic phase is absent after 2.0 mg/kg; the clonic phase is abolished by 10 mg/kg. Ergocornine (0.5-8.0 mg/kg) produces effects on the latency and occurrence of seizure stages similar to those of apomorphine. Piribedil, ET 495 (4-100 mg/kg) is less potent; even after 100 mg/kg clonic and tonic phases occurred in 50% of the mice.

Topics: Acoustic Stimulation; Animals; Apomorphine; Ergolines; Exploratory Behavior; Male; Mice; Mice, Inbred DBA; Motor Activity; Piperazines; Piribedil; Receptors, Drug; Seizures

Four indoleamine antagonists were evaluated for relative potencies as inhibitors of tryptamine-induced forepaw clonus and 5-hydroxytryptophan-evoked head twitches. Methergoline was approximately three times more potent against the forepaw clonus than the head twitch response, whereas methysergide exhibited nearly equal activity in both tests. Cyproheptadine and cinanserin showed a profile opposite to methergoline and a greater degree of selectivity, being 25 to 40 times more potent as inhibitors of the 5-hydroxytryptophan- than of the tryptamine-induced response. These findings clearly demonstrate that the rank order of potency of indoleamine antagonists varies greatly depending upon the test procedure employed.

Topics: 5-Hydroxytryptophan; Anilides; Animals; Cinnamates; Cyproheptadine; Ergolines; Female; Foot; Head; Methysergide; Myoclonus; Rats; Seizures; Sulfides; Tryptamines

Topics: Animals; Ergolines; Escape Reaction; Guinea Pigs; Lysergic Acid Diethylamide; Nicotinic Acids; Seizures

Topics: Animals; Ergolines; Evoked Potentials; Eye Movements; Haplorhini; Light; Lysergic Acid Diethylamide; Methylergonovine; Methysergide; Motor Activity; Muscle Tonus; Myoclonus; Psilocybin; Seizures; Tryptamines