Biomedical subjects

L Turski

Publications and source records attributed to L Turski.

At least 73 records · Page 4Linked to original sources

PubMed1988

Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.

The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non-steroidal anti-inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg/kg (60-174), and phenylbutazone, 59 mg/kg (50-70) converted the non-convulsant dose of pilocarpine, 200 mg/kg, to a convulsant one. Indomethacin, 1-10 mg/kg, and ibuprofen, 10-100 mg/kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22-30) mg/kg, prevented seizures and protected rats from seizure-related brain damage induced by pilocarpine, 380 mg/kg. These results indicate that non-steroidal anti-inflammatory drugs differentially modulate the threshold for pilocarpine-induced seizures.

Animals↗

PubMed1988

Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine.

Intracerebroventricular (i.c.v.) injection of tiletamine, 0.001 mumol, a presumed non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, protected mice from convulsions induced by NMDA and quinolinate, but not from those induced by excitatory amino acids interacting preferentially with non-NMDA receptors. At higher doses, however, tiletamine induced convulsions by itself. Tiletamine-induced convulsions were antagonized by the broad spectrum excitatory amino acid antagonist, gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS), and were potentiated by the competitive NMDA antagonist, 2-amino-7-phosphonohepatanoate (AP7). Intrathecal (i.t.) injection of tiletamine, 0.01-1.0 mumol, dose-dependently suppressed spinal flexor reflexes. Tiletamine, 0.01 and 0.1 mumol, failed to affect spinal Hoffman- (H-) reflexes, whereas tiletamine, 1.0 mumol, led to a 50% increase of the H-reflex amplitude. It is concluded that the anticonvulsant and reflex suppressant action of tiletamine are due to antagonism of NMDA receptor-mediated excitation. The convulsant effect of tiletamine and its excitatory effect on spinal H-reflexes at higher doses, however, appear to be mediated by non-NMDA receptors.

Animals↗

PubMed1988

Delta-aminovaleric acid antagonizes the pharmacological actions of baclofen in the central nervous system.

The action of delta-aminovaleric acid (AVA) on the muscle relaxant properties of baclofen, a GABAB receptor agonist, was investigated in two experimental models: (1) the pathologically increased muscle tone of the gastrocnemius muscle in spastic mutant Han-Wistar rats and (2) the Hoffmann (H)-reflex recorded from plantar foot muscles after electrical stimulation of the tibial nerve in barbiturate (60 mg/kg) anaesthetized rats. In both paradigms coadministration of AVA (500 nmol/5 microliter) antagonized the muscle relaxant action of intrathecally applied baclofen (0.2-2 nmol), but failed to affect the muscle relaxant effects of intrathecally injected muscimol (2-20 nmol). In contrast, coadministration of bicuculline (1 nmol) did block the muscle relaxant action of muscimol, but failed to alter the effects of baclofen. When administered alone, bicuculline (1 nmol), or AVA (500 nmol-2 mumol) were without intrinsic action in both paradigms. In an additional series of experiments we investigated the action of AVA on a supraspinal effect of baclofen. Coadministration of AVA (12.5 nmol/0.5 microliter) in the ventromedial thalamic nucleus antagonized the catalepsy induced by baclofen (ED50 10 pmol/0.5 microliter), as indicated by an increase in ED50 of baclofen by a factor of 4.835 and a parallel shift of the probit-log dosage regression line to the right. The parallel shift seems to be consistent with a competitive mechanism of action of AVA. This study presents evidence that AVA antagonizes central pharmacological actions of baclofen at both spinal and supraspinal sites without affecting the actions of a GABAA agonist, muscimol.

Animals↗

PubMed1988

Catalepsy after microinjection of haloperidol into the rat medial prefrontal cortex.

To investigate the behavioural role of mesocortical dopamine innervation we performed bilateral microinjections of haloperidol into various parts of the rat frontal cortex and into adjacent subcortical forebrain structures. Haloperidol (2.5 micrograms/0.5 microliter) locally injected into the medial prefrontal cortex or into the rostral part of the neostriatum resulted in the development of catalepsy as measured in the bar test. In contrast, injections of haloperidol into the nucleus accumbens, more caudal parts of the neostriatum, anterior cingulate cortex, rostral and lateral parts of the prefrontal cortex and into the lateral ventricles failed to induce catalepsy. It is concluded that blockade of dopamine receptors located in the rostral neostriatum and in the medial prefrontal cortex contributes to the development of haloperidol induced catalepsy.

Animals↗

PubMed1988

Dopamine-sensitive anticonvulsant site in the rat striatum.

The basal ganglia are involved in the organization of movement and function in the initiation and expression of generalized and limbic seizures. Dopamine is the principal neurotransmitter of the mesencephalic efferent pathways terminating in the mammalian striatum. No function has been ascribed to mesostriatal dopamine in the control of seizure spread in the brain. This work presents evidence that bilateral application of picomole amounts of apomorphine (a dopamine agonist) into the striatum confers protection against seizures produced by pilocarpine (a cholinergic agonist) in rats. The anticonvulsant effect of apomorphine is topographically confined to the caudate-putamen, nucleus accumbens, and olfactory tubercle. Bilateral application of nanomolar amounts of haloperidol (a dopamine antagonist) into the caudate-putamen or systemic application of haloperidol both lower the threshold for pilocarpine-induced seizures. Local application of an excitatory amino acid N-methyl-D-aspartate, into the substantia nigra pars compacta, ventral tegmental area, or retrorubral area, sites of origin of mesostriatal dopaminergic pathways, protects rats against seizures produced by pilocarpine. These results suggest that dopaminergic transmission in the striatum may be operative in complex neuronal networks modulating the seizure threshold.

Amino Acids↗

PubMed1987

The susceptibility of rats to pilocarpine-induced seizures is age-dependent.

Behavioral, electroencephalographic and morphological changes induced by systemic administration of pilocarpine hydrochloride were studied in 3-90-day-old rats. Pilocarpine, 100, 200 and 380 mg/kg, presented a characteristic array of behavioral patterns in developing rats. Hyper- or hypoactivity, tremor, loss of postural control, scratching, head bobbing and myoclonic movements of the limbs dominated the behavior in 3-9-day-old rats. No overt motor seizures were observed in this age group. More intense behavioral signs evolving in some animals to limbic seizures and status epilepticus occurred when pilocarpine was administered in 12-day-old-rats. The electrographic activity in these animals progressed from low voltage spiking registered concurrently in the hippocampus and cortex during the first week of life into localized epileptic activity in the hippocampus, which spread to cortical recordings during the second week of life. No morphological alterations were detected in the brains of 3-12-day-old rats subjected to the action of pilocarpine, 100-380 mg/kg. The adult pattern of behavioral and electroencephalographic sequelae after pilocarpine was encountered in 15-21-day-old rats. Akinesia, tremor and head bobbing progressed in 15-21-day-old rats given pilocarpine, 100-380 mg/kg, to motor limbic seizures and status epilepticus. The lethal toxicity of pilocarpine reached 50% during the third week of life. This increased susceptibility to the convulsant action of pilocarpine was characterized by a shortened latency for behavioral and electrographic signs, and an increased severity of seizures relative to older and younger rats. In 15-21-day-old rats subjected to pilocarpine-induced convulsions high voltage fast activity superposed over hippocampal theta-rhythm, progressed into high voltage spiking and spread to cortical records. The electrographic activity became well synchronized and then developed into seizures and status epilepticus. Morphological analysis of frontal forebrain sections in 15-21-day-old rats which underwent status epilepticus after pilocarpine revealed no damage or an attenuated pattern of damage. In 15-21-day-old rats which presented epilepsy-related brain damage, morphological breakdown was seen in the hippocampus, amygdala, olfactory cortex, neocortex and certain thalamic nuclei. No damage was detected in the substantia nigra and lateral thalamic nucleus. An adult pattern of the damage to the brain, in terms of extent and topography, was present in 4-5-week-old rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1987

Substantia nigra and motor control in the rat: effect of intranigral alpha-kainate and gamma-D-glutamylaminomethylsulphonate on motility.

Bilateral microinjections of an excitatory amino acid, alpha-kainate (KA), 5-50 ng, into the substantia nigra pars reticulata (SNR) result in an increase in the muscle tone and catalepsy in rats. The preferential KA/quisqualate antagonist, gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS), 10 micrograms, blocks the actions of KA, 25 ng, when coadministered into the SNR. The chemical lesion of the caudate-putamen with 6-hydroxydopamine (6-OHDA) does not affect either increases in the muscle tone or catalepsy produced by KA, 25 ng, from the SNR. The lesion of the caudate-putamen with ibotenate moderately enhances the effect of KA, 25 ng, on the muscle tone. Microinjections of KA, 25 ng, into the substantia nigra pars compacta (SNC) do not increase the muscle tone and lead to significantly less pronounced catalepsy relative to that observed following the injections of KA into the SNR. Unilateral microinjections of KA, 10-50 ng, into the SNR elicit ipsilateral turning in rats in a dose- and time-dependent manner. Unilateral application of gamma-D-GAMS, 1-10 micrograms, into the SNR produces contralateral turning. The turning evoked by KA, 25 ng, or gamma-D-GAMS, 10 micrograms, is affected neither by 6-OHDA nor by ibotenate lesion of the caudate-putamen. These results demonstrate that excitatory neurotransmission in the substantia nigra participates in the regulation of the muscle tone and posture in rats.

Animals↗

PubMed1987

Microinjections of the gamma-aminobutyrate antagonist, bicuculline methiodide, into the caudate-putamen prevent amygdala-kindled seizures in rats.

We used amygdala-kindled seizures in rats to study the function of striatal gamma-aminobutyrate (GABA) in the regulation of the seizure threshold of the limbic forebrain. Microinjections of the GABAA antagonist, bicuculline methiodide, 1 pmol, into the caudate-putamen protected rats against amygdala-kindled seizures. This result shows that striatal GABA differentially modulates the threshold for limbic seizures.

Amygdala↗

PubMed1987

Evidence that antagonism at non-NMDA receptors results in anticonvulsant action.

The effect of gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS) and 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylate (pBB-PzDA) on convulsions elicited by intracerebroventricular application of kainate (KA) and N-methyl-D-aspartate (NMDA) was studied in mice. gamma-D-GAMS, 0.0025-1.0 mumol, and pBB-PzDA, 0.001-0.2 mumol, were preferentially active against myoclonic seizures induced by kainate, but had also pronounced anticonvulsant action against NMDA. Although pBB-PzDA was a more potent anticonvulsant relative to gamma-D-GAMS, gamma-D-GAMS displayed higher kainate-selectivity. gamma-D-GAMS, 0.025 and 0.5 mumol, and pBB-PzDA, 0.1 mumol, blocked myoclonic seizures induced by kainate in the presence of 2-amino-7-phosphonoheptanoate, a selective antagonist at the NMDA receptor, with potency comparable to that for antagonism of seizures produced by kainate alone. These results indicate that antagonism at kainate receptors may contribute to anticonvulsant drug action.

Animals↗

PubMed1987

Muscle relaxant and anticonvulsant activity of 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a novel N-methyl-D-aspartate antagonist, in rodents.

A novel 4-substituted derivative of piperazine-2-carboxylic acid, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), with potent N-methyl-D-aspartate (NMDA) antagonist activity was evaluated as a muscle relaxant in genetically spastic rats. CPP, 0.02-0.1 mmol/kg, given intraperitoneally reduced the tonic activity in the electromyogram recorded from the gastrocnemius muscle of genetically spastic rats in a dose- and time-dependent manner. Muscle relaxation was also seen following intrathecal application of CPP, 0.0002-0.002 mumol, in genetically spastic rats. CPP, 0.1 mmol/kg, while not affecting Hoffman (H-) reflexes, depressed flexor reflexes in anesthetized rats following intravenous administration. In mice, CPP, 0.001 mumol, given intracerebroventricularly preferentially antagonized myoclonic seizures induced by NMDA and quinolinate, and had no effect on convulsions elicited by kainate, quisqualate and L-glutamate. These observations identify CPP as the most potent preferential NMDA antagonist so far tested with muscle relaxant and anticonvulsant activity resembling the profile of action of 2-amino-7-phosphonoheptanoate.

Animals↗

PubMed1987

Only certain antiepileptic drugs prevent seizures induced by pilocarpine.

Seizures produced in rats by systemically administered pilocarpine (PILO) provide a model for studying the generation and spread of convulsive activity in the forebrain. PILO, 380 mg/kg, induces a sequence of behavioral and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures in humans. The present study was undertaken to determine whether clinically utilized antiepileptic drugs share an ability to suppress seizures and brain damage elicited by PILO in rats. Clonazepam, ED50 0.35 mg/kg (0.25-0.49), phenobarbital, 23.4 mg/kg (18.5-29.6), and valproic acid, 286 mg/kg (202-405), prevented the buildup of limbic seizures and protected against seizure-related brain damage. Pretreatment with trimethadione, 179 mg/kg (116-277), resulted in a moderate protection against PILO-induced seizures, whereas carbamazepine, 10-50 mg/kg, and diphenylhydantoin, 10-200 mg/kg, blocked neither convulsions nor brain damage produced by the drug. Surprisingly, ethosuximide, 196 mg/kg (141-272), and acetazolamide, 505 mg/kg (332-766), both lowered the threshold for seizures induced by PILO and converted a non-convulsant dose of PILO, 200 mg/kg, into a convulsant one. These results indicate that only certain anticonvulsant drugs elevate the threshold for PILO-induced seizures and prevent the occurrence of epilepsy-related brain damage. The resistance of seizures produced by PILO in rats to antiepileptic drugs reaffirms the clinically obvious lack of effective treatments for limbic convulsions.

Animals↗

PubMed1987

Unusual interactions of excitatory amino acid receptor agonists: alpha- and beta-kainate antagonize motor responses to N-methyl-D-aspartate in rodents.

The alpha- and beta-stereoisomers of kainate correspond sterically to the L- and D-isomers of glutamate. Alpha-Kainate is a potent excitant at a specific membrane receptor site (kainate receptor). Beta-Kainate has been proposed as a functional N-methyl-D-aspartate antagonist in vivo. Because of the structural similarities between the alpha- and beta-stereoisomers of kainate we have investigated the interactions of both compounds with N-methyl-D-aspartate-mediated excitation in two well established animal models for assessing the action of excitatory amino acids and their antagonists in vivo: determination of CD50 (convulsant dose) for myoclonic seizures in mice and electromyographic measurement of muscle tone in genetically spastic rats. We find that alpha-kainate and beta-kainate produce myoclonic seizures in mice when given intracerebroventricularly and increase the muscle tone in genetically spastic rats when given intrathecally. Alpha-Kainate is about 5000 times more potent than beta-kainate as a convulsant and about 1000 times more active than beta-kainate in increasing the muscle tone. The excitatory actions of alpha-kainate and of beta-kainate are blocked by gamma-D-glutamylaminomethylsulphonate, a preferential kainate/quisqualate antagonist, but not by (+/-)-2-amino-7-phosphonoheptanoate, a specific N-methyl-D-aspartate antagonist. Surprisingly, alpha-kainate and beta-kainate antagonize the myoclonic seizures and the increase in muscle tone produced by N-methyl-D-aspartate, and potentiate both the anticonvulsant and myorelaxant actions of (+/-)2-amino-7-phosphonoheptanoate. Quisqualate induces myoclonic seizures in mice after intracerebroventricular application and increases muscle tone in genetically spastic rats following intrathecal injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae.

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

PubMed1987

Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen.

We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold. N-Methyl-D-aspartate (N-Me-D-Asp) is an excitatory amino acid derivative that is a powerful convulsant agent when injected into the cerebral cortex, amygdala, or hippocampus in rats. Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizures induced by pilocarpine (injected systemically), with an ED50 of 0.7 nmol (range 0.5-1.0 nmol). Lesioning the caudate-putamen (by bilateral microinjection of the excitotoxin ibotenate) converted subconvulsant doses of pilocarpine into convulsant ones. The anticonvulsant action of N-Me-D-Asp in the caudate-putamen was reversed by blocking gamma-aminobutyrate-mediated inhibition in the substantia nigra pars reticulata or in the entopeduncular nucleus. The results suggest that the caudate-putamen and its gamma-aminobutyrate-dependent efferent pathways modulate the threshold for seizures in the limbic forebrain.

Animals↗

PubMed1986

Motor actions of excitatory amino acids and their antagonists within the rat ventromedial thalamic nucleus.

The present study investigates the role of excitatory amino acid receptors within the rat ventromedial thalamic nucleus (VM) for the mediation of motor behaviour. For this purpose changes of motility were monitored after microinjections of excitatory amino acids and of various excitatory amino acid antagonists into the VM. N-Methyl-D-aspartate (NMDA) and kainate (KA), but not quisqualate (QA), led to a dose-dependent increase of exploratory activity. A specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate (-)-AP7), preferential non-NMDA antagonists, 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylate (pCB-PzDA) and gamma-D-glutamylaminomethylsulphonate (GAMS), and a broad spectrum antagonist, kynurenate (KYN), induced catalepsy in a dose-dependent manner. The catalepsy induced by (-)-AP7 was antagonized by NMDA, but not by KA, the pCB-PzDA-induced catalepsy was blocked by KA, but not by NMDA and the KYN-induced catalepsy was reversed by either NMDA or KA. These data point to a role of both NMDA and KA receptors within the VM for the regulation of motility.

Amino Acids↗

PubMed1986

Seizures produced by pilocarpine: neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrain.

Morphological analysis of brains from rats receiving a convulsant dose of the muscarinic cholinergic agonist, pilocarpine hydrochloride (380 mg/kg), revealed a widespread damage to the forebrain as assessed by light microscopy 5-7 days after seizures. The substantia nigra, olfactory cortex, amygdala, hippocampus, septum, temporal cortex and thalamus underwent prominent morphological injury and cell loss. A concurrent assessment of the activity of L-glutamate decarboxylase (GAD), the gamma-aminobutyrate (GABA) synthesizing enzyme, demonstrated marked deficits in GAD activity in the brain regions undergoing morphological insult. Diazepam, 10 mg/kg, and scopolamine hydrochloride, 10 mg/kg, administered 30 min prior to the injection of pilocarpine, 380 mg/kg, prevented acute behavioral and electrographic, and long-term morphological and biochemical sequelae of seizures. These findings suggest that the muscarinic antagonist, scopolamine, and the anticonvulsant benzodiazepine, diazepam, may aid in preventing extensive brain damage related to pathological muscarinic cholinergic overactivity. The similarity of the topography of the damage and deficits in the GAD activity in brains of rats treated with pilocarpine indicates that GABAergic neurons are lost in the subregions of the brain preferentially sensitive to the convulsant action of pilocarpine.

Animals↗

PubMed1986

Muscle relaxant action of phenobarbitone in genetically spastic rats: an electromyographic study.

The muscle relaxant effect of phenobarbitone was studied in genetically spastic rats which exhibit spontaneous tonic activity in the electromyogram (EMG) of the gastrocnemius muscle. Phenobarbitone, 10-30 mg/kg i.p., reduced the tonic activity in the EMG of the gastrocnemius muscle of such rats in a dose- and time-dependent manner. The GABA antagonists bicuculline, 2 mg/kg i.p., and picrotoxin, 2 and 3 mg/kg i.p., reduced the muscle relaxant effect of phenobarbitone, 20 and 30 mg/kg. The benzodiazepine receptor antagonists, Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg (doses which do not affect tonic activity in the EMG), failed to alter the depressant effect of phenobarbitone 30 mg/kg, in the EMG. Beta-Carboline-3-carboxylic acid methylester (beta-CCM), 2 mg/kg i.p., while not affecting the tonic activity in the EMG, reversed the depressant effect of phenobarbitone, 30 mg/kg. Both Ro 15-1788, 5 mg/kg, and CGS 8216, 5 mg/kg, prevented the reversal of the depressant action of phenobarbitone, 30 mg/kg, produced by beta-CCM, 2 mg/kg. The results indicate that the muscle relaxant action of phenobarbitone in genetically spastic rats is mediated via GABA-related mechanisms and add further support to the hypothesis that both Ro 15-1788 and CGS 8216 are specific antagonists at benzodiazepine receptors, devoid of intrinsic activity at moderate doses. The results also suggest that reversal of the muscle relaxant action of phenobarbitone by beta-CCM is mediated via a GABA/benzodiazepine receptor/chloride ionophore complex.

Animals↗

PubMed1986

Substantia nigra and entopeduncular nucleus: supraspinal sites of the muscle relaxant action of tizanidine.

Microinjection of tizanidine into the substantia nigra pars reticulata or entopeduncular nucleus reduces muscle tone in genetically spastic rats. The effect of tizanidine is related to alpha 2-adrenergic mechanism since yohimbine, an alpha 2-adrenergic antagonist, and not prazosin, an alpha 1-adrenergic antagonist, attenuates the muscle relaxation produced by the drug. These results signify basal ganglia output stations as possible sites whereby tizanidine acting via alpha 2-adrenergic mechanism exerts its muscle relaxant action.

Animals↗