strychnine and Movement-Disorders

Dyskinetic, writhing-like movements, similar to those produced in mice after an intraperitoneal (IP) injection of acetic acid, were elicited by intrathecal (IT) injection of GABA, glycine, taurine or beta-alanine. Baclofen and muscimol failed to produce this behavior. While acetic acid-induced writhing is inhibited by narcotic and nonnarcotic compounds, GABA-induced writhing was found to be insensitive to pretreatment with either morphine or capsaicin. Moreover, acetic acid-induced writhing does not appear to involve GABAergic transmission as IT injections of nipecotic acid did not alter the intensity of response to IP acetic acid while it enhanced the response to IT GABA. Writhing induced by glycine was not inhibited by strychnine at subconvulsive doses, suggesting that it involves an action at strychnine-insensitive receptors. Together these data suggest that while the dyskinetic movements produced by inhibitory amino acids do not appear to reflect an alteration in nociception, they may mimic either the motor response to abdominal pain or spasticity.

Topics: Alanine; Animals; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Glycine; Injections, Intraperitoneal; Injections, Spinal; Male; Mice; Morphine; Movement Disorders; Naloxone; Strychnine; Taurine; Time Factors

Topics: Acetylcholine; Administration, Oral; Animals; Anura; Blood Pressure; Cats; Central Nervous System Stimulants; Depression, Chemical; Drug Synergism; Fusidic Acid; Gastrointestinal Motility; Injections, Intravenous; Mice; Motor Activity; Movement Disorders; Muscle Contraction; Muscle, Smooth; Nervous System; Neuromuscular Nondepolarizing Agents; Nictitating Membrane; Pentylenetetrazole; Rabbits; Rats; Seizures; Strychnine; Vagus Nerve

1. The drug HA-966 (1-hydroxy-3-amino-pyrrolidone-2), which chemically resembles the cyclic form of GABA, has been studied for neuro-pharmacological properties and for effects on the catecholamine content of the corpus striatum.2. The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA-966 caused periodical sleeping episodes.3. The exploratory behaviour and the amphetamine-induced motor activity in mice were blocked by HA-966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA-966 differs from neuroleptics.4. Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA-966. The muscarinic effects of tremorine were not reduced by HA-966, indicating a selective central antitremor effect.5. HA-966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA-966 depresses central internuncial neurones.6. In rats and rabbits HA-966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between ;sleep-EEG' and behaviour.7. In rat brain, HA-966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5-hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with alpha-methyl-p-tyrosine.8. Several effects of intravenously administered HA-966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA-966 is converted to a pharmacologically active metabolite.9. The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA-related hypothesis as to the mode of action of HA-966 is presented.

Topics: Acoustic Stimulation; Amines; Amphetamine; Animals; Basal Ganglia Diseases; Behavior, Animal; Brain Chemistry; Cats; Corpus Striatum; Dogs; Dopamine; Electroencephalography; Exploratory Behavior; Hepatectomy; Male; Mice; Motor Activity; Movement Disorders; Nicotine; Pyrrolidinones; Rabbits; Rats; Reflex; Strychnine; Tremor; Tremorine

Topics: Anesthesia; Animals; Brain Stem; Cats; Cerebral Cortex; Electric Stimulation; Electrophysiology; Hindlimb; Inflammation; Mesencephalon; Movement Disorders; Neurons; Pyramidal Tracts; Reflex; Reflex, Monosynaptic; Sciatic Nerve; Spinal Cord; Strychnine; Synapses; Thalamus

Topics: Hyperkinesis; Movement Disorders; Skin Diseases; Strychnine