strychnine and Acute-Disease

Glycinergic neurons in the spinal dorsal horn have been implicated in the inhibition of spinal pain processing in peripheral inflammation and chronic pain states. Neuronal isoform glycine transporter-2 (GlyT2) reuptakes presynaptically released glycine and regulates the glycinergic neurotransmission. In this study, we examined whether a selective GlyT2 inhibitor, ALX1393, elicits an antinociceptive effect in a rat acute pain model.. Male Sprague-Dawley rats were implanted with a catheter intrathecally. The effects of intrathecal administration of ALX1393 (4, 20, or 40 microg) on thermal, mechanical, and chemical nociception were evaluated by tail flick, hot plate, paw pressure, and formalin tests. Furthermore, to explore whether ALX1393 affects motor function, a rotarod test was performed.. ALX1393 exhibited antinociceptive effects on the thermal and mechanical stimulations in a dose-dependent manner. The maximal effect of ALX1393 was observed at 15 min after administration, and a significant effect lasted for about 60 min. These antinociceptive effects were reversed completely by strychnine injected immediately after the administration of ALX1393. In the formalin test, ALX1393 inhibited pain behaviors in a dose-dependent manner, both in the early and late phases, although the influence was greater in the late phase. In contrast to antinociceptive action, ALX1393 did not affect motor function up to 40 microg.. This study demonstrates the antinociceptive action of ALX1393 on acute pain. These findings suggest that the inhibitory neurotransmitter transporters are promising targets for the treatment of acute pain and that the selective inhibitor of GlyT2 could be a novel therapeutic drug.

Topics: Acute Disease; Analgesics; Animals; Dose-Response Relationship, Drug; Glycine Plasma Membrane Transport Proteins; Injections, Spinal; Male; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Rotarod Performance Test; Serine; Strychnine

Isovaline, a nonproteinogenic alpha-amino acid rarely found in the biosphere, is structurally similar to the inhibitory neurotransmitters glycine and gamma-aminobutyric acid. Because glycine(A) and gamma-aminobutyric acid receptor agonists are antiallodynic, we hypothesized that isovaline produces antinociception in mice.. All experiments were performed on female CD-1 mice using a blinded, randomized, and controlled design. The effects of RS-isovaline were studied on nociceptive responses to (1) formalin injection into the hindpaw; (2) glutamate injection into the hindpaw; and (3) strychnine injection either into the lumbar intrathecal space or cisterna magna. We determined the effects of IV RS-isovaline (50, 150, or 500 mg/kg; n = 10/dose) or intrathecal RS-, R-, and S-isovaline, glycine, and beta-alanine into the lumbar intrathecal space (5-microL volumes of 60, 125, 250, and 500 mM; n = 9/dose/group) on the response to formalin in the paw. The response to 20 microL intraplantar glutamate (750 mM) was compared with glutamate (750 mM) coadministered with isovaline. We also determined the response to intraplantar strychnine. Lumbar intrathecal (100 microM) or intracisternal (200 microM) injections of strychnine into the lumbar intrathecal space or the cisterna magna were used to induce allodynia as a measure of glycine inhibitory dysfunction. The effects of intrathecal or intracisternal strychnine were compared with isovaline coapplied with the strychnine (n = 8/group).. In the formalin paw test, IV isovaline did not change phase I but decreased phase II responses in a dose-dependent manner (50% effective dose = 66 mg/kg, n = 10, P < 0.01). There was no effect on rotarod performance, appearance, or behavior of the mouse, and no respiratory depression. Intrathecal isovaline, glycine, and beta-alanine attenuated phase I and II responses (P < 0.01 for each drug). In contrast to beta-alanine and glycine, isovaline at maximally effective doses did not produce scratching, biting, or agitation. Intrathecal RS- and S-isovaline attenuated phase I (P < 0.05 for each group) and RS-, R-, and S-isovaline attenuated phase II responses (P < 0.05 for each group), with no significant difference between the efficacies of R- and S-enantiomers. Localized strychnine-induced glycine inhibitory dysfunction was greatly reduced by intracisternal (P < 0.01) and intrathecal (P < 0.01) isovaline. Although intraplantar strychnine did not induce peripheral allodynia, high doses of isovaline did not block the peripheral allodynia induced by glutamate.. Isovaline reduced responses in mouse pain models without producing acute toxicity, possibly by enhancing receptor modulation of nociceptive information.

Topics: Acute Disease; Analgesics, Non-Narcotic; Animals; beta-Alanine; Chronic Disease; Cisterna Magna; Female; Formaldehyde; Glutamic Acid; Glycine; Hypnotics and Sedatives; Injections; Injections, Intravenous; Injections, Spinal; Mice; Models, Molecular; Pain; Pain Measurement; Postural Balance; Receptors, Glutamate; Strychnine; Valine

In most severe cases of strychnine poisoning, the patient dies before reaching the hospital. This report describes the treatment and successful outcome of a patient who had taken a dose of strychnine that would normally be fatal. A 28-y-old man was admitted 2 h after ingestion of 1 to 1.5 g of strychnine. He had a Glasgow Coma Score of 14/15 and was severely agitated and in mild respiratory distress; blood pressure was 90/60 mmHg, pulse 110/min, and peripheral pulses weak. He had generalized hyperactive reflexes and had several generalized tonic-clonic convulsions in the emergency department. Treatment consisted of gastric lavage with water, oral administration of activated charcoal and sorbitol solution, continuous intravenous administration of midazolam and then sodium thiopental, furosemide, sodium bicarbonate and hemodialysis for acute renal failure. His clinical course included respiratory distress, agitation, generalized tonic-clonic convulsions, hyperactivity, oliguria and acute tubular necrosis prior to recovery in 23 days. This patient ingested what would normally be a fatal amount of strychnine, had signs and symptoms of severe toxicity and recovered, suggesting that with aggressive supportive care patients may have favorable outcomes.

Topics: Acute Disease; Adult; Blood Chemical Analysis; Diagnosis, Differential; Emergency Treatment; Humans; Male; Poisoning; Strychnine

We examined the influence of lumbosacral glycinergic neurons on the spinobulbospinal and spinal micturition reflexes. Female rats were divided into intact rats, rats with acute injury to the lower thoracic spinal cord (SCI), and rats with chronic SCI. Under urethane anesthesia, isovolumetric cystometry was performed in each group before and after intrathecal (IT) injection of glycine or strychnine into the lumbosacral cord level. The glutamate and glycine levels of the lumbosacral cord were measured after injection of glycine or strychnine in intact and chronic SCI rats. Expression of strychnine-sensitive glycine receptor alpha-1 (GlyR alpha1) mRNA in the lumbosacral cord was also assessed in both rats. In chronic SCI rats, the interval and amplitude of bladder contractions were shorter and smaller when compared with intact rats. IT glycine (0.1-100 microg) prolonged the interval and decreased the amplitude of bladder contractions in both intact rats and chronic SCI rats. IT strychnine (0.01-10 microg) elevated the baseline pressure in intact rats and induced bladder contraction in acute SCI rats. On amino acid analysis, IT glycine (0.01-100 microg) decreased the glutamate level of the lumbosacral cord in intact rats, but not in chronic SCI rats. The glycine level of the lumbosacral cord was 54% lower in chronic SCI rats when compared with intact rats, while the GlyR alpha1 mRNA level did not change after SCI. These results suggest that glycinergic neurons may have an important inhibitory effect on the spinobulbospinal and spinal micturition reflexes at the level of the lumbosacral cord.

Topics: Acute Disease; Animals; Chronic Disease; Disease Models, Animal; Female; Glutamic Acid; Glycine; Glycine Agents; Injections, Spinal; Lumbosacral Region; Rats; Rats, Sprague-Dawley; Receptors, Glycine; Reflex; RNA, Messenger; Spinal Cord; Spinal Cord Injuries; Strychnine; Urinary Bladder; Urination

An 18-year-old female who accidentally ingested strychnine developed chemical pancreatitis in addition to the classical clinical picture of strychnine poisoning. Many drugs or chemicals have been reported to be associated with pancreatitis; however, this paper provides us with the first evidence that acute pancreatitis may follow strychnine poisoning. The patient survived despite the development of seizures, lactic acidosis, rhabdomyolysis, and pulmonary infiltrates. Toxicology testing confirmed the presence of strychnine in blood (2.17 mg/L), gastric aspirate, and urine. Attention is drawn to the fact that survival can follow the ingestion of large doses of strychnine providing there is no delay in diagnosis and treatment. The pathophysiologic mechanism of chemical pancreatitis is discussed.

Topics: Acute Disease; Adolescent; Creatine Kinase; Female; Humans; L-Lactate Dehydrogenase; Pancreatitis; Poisons; Seizures; Strychnine

Strychnine competes with the inhibitory neurotransmitter glycine producing an excitatory state characterized clinically by hyperreflexia, severe muscle spasms, and convulsions. However, the kinetics after overdose have not been well described.. A 34 year-old male presented to the emergency department 20 minus after ingesting half of a 250-mL container of 2% strychnine sulfate (2.25 g). The reported lethal dose is 100-120 mg. He was alert and oriented and experiencing muscle spasms. His condition deteriorated prompting sedation, muscle paralysis, and tracheal intubation. He was given activated charcoal 100 g per nasogastric tube. He was admitted to intensive care where he was managed with diazepam, pentobarbital, and pancuronium. Despite mild rhabdomyolysis, he recovered and was extubated on day three. Although receiving prophylactic heparin therapy, a massive fatal pulmonary embolus ensued. Eighteen blood specimens for strychnine analysis were obtained from 20 minutes to 51 hours after ingestion. Serum concentrations were determined with gas chromatography-mass spectroscopy. Disappearance followed a first-order process with a t 1/2 of 16 hours (r, = 0.97).. Our results confirm the findings of an earlier case report of 19 strychnine levels obtained between 4 and 19 hours which described first-order kinetics with a similar t 1/2 of 10 hours.. Strychnine disappearance in this overdose was well described by a first-order process with a t 1/2 of 10-16 hours.

Topics: Acute Disease; Adult; Fatal Outcome; Gas Chromatography-Mass Spectrometry; Glycine Agents; Half-Life; Humans; Male; Poisoning; Pulmonary Embolism; Strychnine

Although rare today, poisoning from strychnine, both intentional and accidental, still occurs. A fatal case of self-poisoning with a strychnine preparation is presented. The case illustrates the dramatic presentation of strychnine poisoning, its rapidity of action, and the need for early aggressive treatment. The discussion centers on the pharmacokinetics, the mechanism of action, the signs and symptoms, and the treatment of poisoning from strychnine. The need for rapid diagnosis and the current recommended therapy for this poison are discussed.

Topics: Acute Disease; Humans; Male; Middle Aged; Strychnine

Effect of diazepam on the activity of the epileptic complex consisting of a number of foci created with strychnine applications to the brain cortex under conditions of intact brain and at different levels of it neuronal isolation was studied in acute and chronic experiments on cats. It was shown that in the preparations of cerveau isolé and cortex isolé a more rapid formation of the epileptic complex under the influence of the determinant focus, and marked generalizaiton of convulsant activity could be observed. Diazepam induced a decrease in the amplitude and frequency of convulsive discharges. There was a break in the synchronization of their appearance first in the dependent foci and then in the determinant one. The diazepam effects were seen both in the intact brain and in the preparations of cerveau isolé and cortex isolé. These findings indicate that diazepam may exert an indirect action on the brain cortex that does not exclude the participation of other brain structures in the realization of the diazepam effect under conditions of intact brain.

Topics: Acute Disease; Animals; Cats; Cerebral Cortex; Decerebrate State; Diazepam; Electrophysiology; Seizures; Strychnine

Foci of increased excitability were created in acute experiments on rats by means of weak strychnine solutions working at independent regimens. The hyperactive excitability focus induced by means of concentrated strychnine solutions played the role of a determinant structure. The importance of the latter is in the fact that it determines the activity character of other epileptogenic foci, enhances their convulsive activity, unites them into a single functional complex and determines the behaviour of the complex as a whole. This complex can be destroyed by depression of the determinant focus activity. Switching off any dependent foci included into this complex fails to destroy that latter. Results of the investigations confirmed on the new model the general concept of the role played by the determinant structures in the brain activity.

Topics: Acute Disease; Animals; Cerebral Cortex; Disease Models, Animal; Electroencephalography; Epilepsies, Partial; Evoked Potentials; Rats; Seizures; Strychnine

Topics: Acute Disease; Animals; Cats; Dendrites; Motor Cortex; Seizures; Strychnine