strychnine and tramiprosate

In experiments in which mice were placed with their forelegs over a 4 cm high horizontal bar, pretreatment with delta-9-tetrahydrocannabinol (THC; 10 mg/kg i.p.) significantly delayed descent from the bar. This response to THC was markedly enhanced by doses of amino-oxyacetic acid, flurazepam, cis(Z)-flupentixol, muscimol, (-)-baclofen and NO-328 having little or no effect when given alone. No synergism was detected between THC and (+)-baclofen or trans(E)-flupentixol. The interactions between THC and flurazepam, amino-oxyacetic acid and NO-328 were attenuated by (+)-bicuculline and by homotaurine, but not by strychnine. The interaction between THC and (-)-baclofen was prevented by homotaurine but not by (+)-bicuculline whereas only (+)-bicuculline reduced the interactions of THC with muscimol and cis(Z)-flupentixol. Flumazenil prevented the interaction between THC and flurazepam but not that between THC and NO-328. The results suggest that the synergistic interactions observed in this study depended on the activation of GABAA and/or GABAB receptors, probably located in extrapyramidal GABAergic pathways.

Topics: Aminooxyacetic Acid; Animals; Baclofen; Bicuculline; Catalepsy; Dronabinol; Drug Synergism; Flumazenil; Flupenthixol; Flurazepam; GABA Antagonists; gamma-Aminobutyric Acid; Male; Mice; Muscimol; Nipecotic Acids; Receptors, GABA-A; Strychnine; Taurine; Tiagabine

The light-evoked release of [3H]acetylcholine (ACh) from the rabbit retina in vivo was measured and taken as an index of cholinergic amacrine cell activity. The light-evoked release of [3H]ACh was reduced by locally applied gamma-aminobutyric acid (GABA), muscimol and 3-aminopropanesulphonic acid (3-APS). The concentrations of these drugs which reduced the light-evoked release of [3H]ACh by 50% (EC50) were 900, 0.3 and 5 microM respectively. In contrast, (-)-baclofen (5 mM), but not (+)-baclofen, significantly increased the light-evoked release of [3H]ACh. The GABA antagonist, bicuculline increased the resting release of [3H]ACh but abolished the inhibitory action of muscimol on the light-evoked release of [3H]ACh. Glycine and taurine also reduced the light-evoked release of [3H]ACh from the retina, their EC50 values being 1.5 and 0.3 mM respectively. This action was blocked by strychnine, but not by bicuculline. In contrast to the GABA antagonist, strychnine did not affect the spontaneous resting release of [3H]ACh. Retinal [3H]ACh release was not affected by dopamine, 5-hydroxytryptamine (5-HT) morphine, substance P, somatostatin, cholecystokinin sulphate, thyrotropin releasing hormone, luteinizing hormone releasing hormone or angiotensin. Electroretinographic changes produced by amino acids and GABA agonists involved mainly the b-wave and were not correlated with their effects on ACh release. Thus, GABA increased the b-wave amplitude, 3-APS had no effect, whilst muscimol, taurine and glycine either had no effect, or reduced the b-wave amplitude. No obvious changes in the e.r.g. were produced by baclofen, dopamine, 5-HT, morphine or any of the peptides studied with the exception of somatostatin, which reduced the amplitude of the b-wave. It is concluded that cholinergic amacrine cell activity in the rabbit retina may be affected by inputs from other amacrines using GABA or glycine (taurine) as their transmitters, but probably not by inputs from peptidergic or dopaminergic amacrine cells. Our experiments do not provide evidence on the sites of action of GABA, glycine or taurine but the action of bicuculline on the resting release of ACh implies that the activity of the cholinergic amacrine cells is affected by a tonically active GABAergic input.

Topics: Acetylcholine; Animals; Baclofen; Electroretinography; GABA Antagonists; gamma-Aminobutyric Acid; Glycine; Muscimol; Neurotransmitter Agents; Photic Stimulation; Rabbits; Retina; Strychnine; Taurine

Young chickens with inefficient blood-brain barrier were employed to study the effects of aliphatic omega-aminosulfonic acids with varying numbers of carbon chains on the central nervous system. Each of the amino acids was intraperitoneally administered to unrestrained and unanesthetized animals, to investigate its effects upon their behavior and electroencephalogram (EEG). omega-Amino acid with a short-chain structure (3-aminopropanesulfonic acid) had a depressing effect similar to that of gamma-aminobutyric acid which is known as a depressant amino acid. On the other hand, the omega-amino acids with long-chain structure (5-aminopentanesulfonic acid and 6-guanidinohexanesulfonic acid) acted as excitants, induced convulsions and developed typical biphasic spikes with high amplitudes in the EEG. The spikes appeared early, and could be detected at the excitant stage before convulsion. In contrast, with the administration of convulsant drugs, the spikes appeared only after the occurrence of convulsion. However, a high dose (1-9 g/kg) of the omega-amino acids was needed to develop their effects. These results suggest that young chickens are valuable in clarifying the characteristic behavior and the brain electrical activity of omega-amino acids. But the omega-amino acids cannot easily pass through the blood-brain barrier in young chicken.

Topics: Alkanesulfonates; Alkanesulfonic Acids; Animals; Behavior, Animal; Central Nervous System Depressants; Central Nervous System Stimulants; Chickens; Electroencephalography; gamma-Aminobutyric Acid; Pentylenetetrazole; Picrotoxin; Structure-Activity Relationship; Strychnine; Taurine; Tubocurarine

The effects of the possible metabolites of taurine--taurocyamine and hypotaurine--and of homotaurine on spike discharge frequency of guinea pig cerebellar Purkinje cells were investigated in comparison with taurine and GABA. Taurocyamine, hypotaurine and homotaurine all dose-dependently suppressed the spike frequency with potencies relative to taurine (ED50 = 1.0 mM) of 6, 0.5 and 500, respectively. Both picrotoxin and strychnine competitively blocked the inhibition by all the substances tested, except for the non-competitive antagonism by picrotoxin on taurocyamine. The sites sensitive to taurocyamine and hypotaurine were situated primarily in the dendritic region of the cerebellar molecular layer, while those to homotaurine were primarily near the Purkinje cell soma. The onset of the inhibitory action of taurine and related sulfur-containing substances was found to be slower than that of GABA.

Topics: Animals; Cerebellum; Culture Techniques; Evoked Potentials; gamma-Aminobutyric Acid; Guanidines; Guinea Pigs; Interneurons; Neural Inhibition; Picrotoxin; Purkinje Cells; Strychnine; Taurine

The central cardiovascular effects of taurine were compared with those of homotaurine and muscimol. The drugs were injected i.c.v. in cumulative doses into pentobarbital-anesthetized cats. Muscimol (0.1-30 microgram/kg) produced dose-dependent hypotension and bradycardia, with a maximum effect of 70 +/- 5 mm Hg and 75 +/- 5 beats/min, respectively. Homotaurine led to a dose-related fall in blood pressure and heart rate; maximum effects were obtained with 300 microgram/kg and averaged 55 +/- 3 mm Hg and 73 +/- 3 beats/min. For both drugs, the dose-response curves were shifted to the right by pretreatment with 10 microgram/kg of bicuculline i.c.v. This antagonism confirms that the central cardiovascular effects of muscimol and homotaurine are mediated by a stimulation of gamma-aminobutyric acid receptors. Taurine produced dose-related hypotension and bradycardia. The depressive effects of taurine started at a dose of 10 microgram/kg; at a dose of 1000 microgram/kg, the maximum effects observed were a 55 +/- 7 mm Hg hypotension and a 53 +/- 8 beats/min bradycardia. These effects were not affected by bicuculline pretreatment, but strychnine (i.c.v) prevented the effects of taurine. These findings indicate that glycine-type receptors may be involved in the taurine effects rather than gamma-aminobutyric acid type receptors. However, these results do not exclude the involvement of taurine-type receptors for which the specific antagonists is not yet available.

Topics: Animals; Bicuculline; Cats; Central Nervous System; Hemodynamics; Injections, Intraventricular; Muscimol; Oxazoles; Strychnine; Taurine