strychnine and Paralysis

In vitro effects of VD-99-11 were examined using adult Angiostrongylus cantonensis and isolated frog rectus. In A. cantonensis, paralysis was elicited by VD-99-11 at 10(-9)-10(-6) g/ml. The paralysis caused by VD-99-11 (10(-8) g/ml) was antagonized by picrotoxin or bicuculline but not by phentolamine. A relationship between VD-99-11 and gabergic antagonists was observed in worm preparations contracted by eserine or pyrantel: VD-99-11 at higher concentrations (3x10(-6) g/ml) caused a marked contraction. In worm preparations contracted with eserine or pyrantel, the only additional contraction induced by VD-99-11 (5x10(-6) g/ml) was antagonized by strychnine. In experiments on the guanidine (2.5x10(-3) M)-induced twitch responses in isolated frog rectus, marked stimulation was caused by VD-99-11 (3-5x10(-6) g/ml). The stimulated responses induced by VD-99-11 were antagonized by tetrodotoxin, D-tubocurarine, strychnine, and hemicholinium-3, respectively. These results suggest that VD-99-11 seems superior to milbemycin D, milbemycin oxime, and ivermectin in some aspects, such as in vitro potency, though this new substance is similar to these drugs in having two different actions on the gabergic mechanism at lower concentrations and on the cholinergic mechanism at higher concentrations.

Topics: Angiostrongylus cantonensis; Animals; Antinematodal Agents; Bicuculline; Female; Guanidine; Guanidines; Hemicholinium 3; In Vitro Techniques; Macrolides; Muscle Contraction; Muscle, Skeletal; Paralysis; Phentolamine; Physostigmine; Picrotoxin; Pyrantel; Rats; Rats, Wistar; Strychnine; Sympatholytics

Selected examples from three series of isomeric (alkylthio)-1,2,4-triazoles were prepared and examined for anticonvulsant activity versus strychnine-, maximal-electroshock-, pentylenetetrazole-, and 3-mercaptopropionic-acid-induced seizures in mice. A number of 5-aryl-3-(alkylthio)-4H-1,2,4-triazoles were selective antagonists of strychnine-induced convulsions. The isomeric 3-aryl-5-(alkylthio)- and 5-aryl-3-(alkylthio)-1H-1,2,4-triazoles were essentially inactive as anticonvulsants. The most potent antagonist of strychnine-induced convulsions was 5-(2-fluorophenyl)-4-methyl-3-(methylthio)-4H-1,2,4-triazole (3s), while the most selective antagonist was 5-(3-fluorophenyl)-4-methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3aa). The anticonvulsant profiles of these 4H-1,2,4-triazoles suggested that they were acting functionally like glycine receptor agonists. Since it has recently been postulated that compounds possessing glycine-agonist-like properties might be useful in the treatment of spasticity, we examined 5-phenyl-4-methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3c) in an in vivo model of spasticity. In this regard, 3c reduced the occurrence of hyperreflexia in rats that had received spinal transections 5-10 weeks previously. While triazole 3c appeared to possess glycine-agonist-like properties in vivo, it did not displace [3H]strychnine binding from rat brain stem/spinal cord membranes in vitro. On the other hand, 3c enhanced muscimol-stimulated 36Cl influx in a rat cerebellar membrane preparation, indicating a possible interaction of these triazoles with the GABAA receptor.

Topics: Animals; Anticonvulsants; Cerebellum; Cerebral Cortex; Chlorides; Electroshock; Flumazenil; Male; Mice; Molecular Structure; Muscle Spasticity; Paralysis; Rats; Rats, Sprague-Dawley; Seizures; Structure-Activity Relationship; Strychnine; Triazoles

Dynorphin A(1-13) administered intrathecally to rats induces a reversible hindlimb paralysis and permanent loss of the tail-flick reflex in a dose-dependent and all-or-none manner. The loss of the tail-flick reflex has been determined to result from neurotoxicity linked to the N-methyl-D-aspartate (NMDA) receptor. Recently, it has been reported that NMDA antagonists attenuate irreversible paralysis induced by dynorphin A(1-17) and dynorphin A(2-17). In the present studies, we examined whether repeated injections of dynorphin A(1-13) acetate salt could change the characteristics of the reversible paralysis. Injections repeated every 48 h resulted in hindlimb paralysis upon each injection which was not different in terms of magnitude or duration (P greater than 0.60). Injections repeated at 2 h intervals resulted in desensitization of the paralytic effects (P less than 0.05). We also examined if strychnine sulfate, a glycine antagonist would alter the paralytic response to dynorphin. Strychnine protected rats from paralysis (P less than 0.01) and loss of the tail-flick reflex with an ED50 of 7 nmol. We conclude that the reversible paralysis induced by dynorphin A(1-13) is repeatable which suggests that the paralysis results from nontoxic or subtoxic actions of dynorphin. Desensitization to the paralytic effects occurs with closely spaced injections by some unknown mechanism. In addition, we conclude that the spinal glycinergic inhibitory system may participate in the induction of the paralysis because strychnine antagonizes dynorphin-induced paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Dose-Response Relationship, Drug; Dynorphins; Male; Narcotics; Paralysis; Peptide Fragments; Rats; Rats, Inbred Strains; Reaction Time; Reflex; Strychnine

Effect of intravenous administration of GABA antagonists on gastric acid secretion in perfused stomachs was studied in rats anesthetized with urethane. Bethanechol (BeCh)-stimulated acid secretion was definitely inhibited by bicuculline, a GABA antagonist, and strychnine, a glycine antagonist, but not by picrotoxin and pentylenetetrazol, GABA antagonists. The inhibitory effect of bicuculline and strychnine was accompanied by vigorous convulsions. Only the bicuculline-induced inhibition was still seen in d-tubocurarine paralyzed rats, and it was abolished in spinal rats. 2-Deoxy-D-glucose (2-DG)-stimulated acid secretion was apparently depressed by all the GABA antagonists of bicuculline, picrotoxin and pentylenetetrazol. The inhibitory effect of picrotoxin, but not bicuculline, on the 2-DG stimulation was still elicited in spinal rats. Inhibition of acid secretion stimulated by pentobarbital, a centrally acting secretagogue, was produced by picrotoxin and pentylenetetrazol in spinal rats. These findings suggest that bicuculline acts centrally to inhibit acid secretion stimulated both peripherally by BeCh and centrally by 2-DG, besides nonspecific mechanisms due to convulsions, and the action would be directed to centers which are implicated in stimulation of the sympatho-adrenomedullary system; picrotoxin and pentylenetetrazol also act centrally to inhibit 2-DG- or pentobarbital-stimulated acid secretion through depression of the central vagal tone which leads to inhibition of gastric acid secretion.

Topics: Animals; Bethanechol Compounds; Bicuculline; Deoxyglucose; GABA Antagonists; Gastric Acid; Injections, Intravenous; Male; Paralysis; Pentylenetetrazole; Picrotoxin; Rats; Rats, Inbred Strains; Spinal Cord Injuries; Stomach; Strychnine; Tubocurarine

Topics: Alkaloids; Animals; Guinea Pigs; Humans; Mice; Neuromuscular Junction; Paralysis; Pentobarbital; Plants, Medicinal; Rats; Seizures; Skin; Strychnine

Topics: Animals; Anticonvulsants; Behavior, Animal; Biotransformation; Central Nervous System; Dose-Response Relationship, Drug; Glycols; Mice; Motor Activity; Paralysis; Propranolol; Seizures; Strychnine; Time Factors

Topics: Aging; Aminopyrine; Anesthesia; Aniline Compounds; Animals; Body Weight; Cytochromes; Electron Transport; Hexobarbital; In Vitro Techniques; Mice; Microsomes, Liver; Nitrobenzenes; Oxidoreductases; Paralysis; Strychnine; Zoxazolamine

Topics: Animals; Mephenesin; Mice; Paralysis; Phenobarbital; Plants, Medicinal; Pyrans; Reflex; Seizures; Strychnine

Topics: Animals; Benzopyrenes; Chromatography, Thin Layer; Fluorometry; Ketones; Liver; Male; Methylcholanthrene; Mixed Function Oxygenases; Oxidoreductases; Paralysis; Phenols; Rats; Strychnine; Time Factors; Zoxazolamine

Topics: Anesthetics; Animals; Antidotes; Ataxia; Electromyography; Isonicotinic Acids; Male; Mephenesin; Mice; Muscle Relaxants, Central; Paralysis; Phenobarbital; Rabbits; Seizures; Strychnine; Tetanus; Tetanus Toxin

Topics: Anesthesia; Animals; Carcinoma 256, Walker; Carisoprodol; Cholinesterase Inhibitors; Female; Injections, Intraperitoneal; Liver; Male; Paralysis; Phenobarbital; Rats; Sex Factors; Statistics as Topic; Strychnine; Zoxazolamine

Topics: Aging; Anesthesia; Animals; Carisoprodol; Female; Hexobarbital; Injections, Intraperitoneal; Insecticides; Liver; Male; Microsomes; Paralysis; Pentobarbital; Pharmaceutical Preparations; Phenobarbital; Rats; Sex Factors; Strychnine; Time Factors; Zoxazolamine

Topics: Action Potentials; Anesthesia; Animals; Autonomic Agents; Cats; Caudate Nucleus; Chloralose; Decerebrate State; Drug Antagonism; Electroencephalography; Electroshock; Imidazoles; Male; Mice; Motor Activity; Paralysis; Pentylenetetrazole; Pyrimidines; Rabbits; Reflex; Respiration, Artificial; Seizures; Spinal Cord; Stimulation, Chemical; Strychnine; Zoxazolamine

Topics: Amides; Anesthesia; Animals; Barbiturates; Body Weight; Carisoprodol; Diphosphates; Female; Hexobarbital; Kidney; Liver; Male; Organ Size; Paralysis; Pentobarbital; Phenobarbital; Rats; Starvation; Strychnine; Sucrose; Zoxazolamine

Topics: Animals; Cats; Electrophysiology; Heterocyclic Compounds; Muscle Spindles; Neuromuscular Junction; Paralysis; Parasympathomimetics; Physostigmine; Pilocarpine; Piperidines; Seizures; Strychnine; Synapses; Tachyphylaxis

Topics: Animals; Fractures, Bone; Paralysis; Rabbits; Seizures; Spinal Cord Injuries; Strychnine

Topics: Alkaloids; Animals; Birds; Cats; Cochlear Nerve; Cordotomy; Electric Stimulation; Electrocardiography; Electroencephalography; Gallamine Triethiodide; Paralysis; Pharmacology; Piperidines; Research; Seizures; Spinal Cord; Strychnine; Toxicology