Convulsant toxins

The convulsant toxins, tetanus toxin (cause of wound tetanus) and strychnine diminish the efficacy of interneuronal synaptic inhibition mediated by the amino acid glycine (A). As a consequence of an unrestrained spread of nerve impulses in the spinal cord, motor convulsions develop. The involvement of respiratory muscle groups endangers life. 

The bufogenins responsible for the heart activity with positive inotropic effect, and the bufotoxins acting as convulsive toxins, need not be mentioned further in this context (ref.3) as they do not possess a remarkable growth inhibition effect on microorganisms. Research in this field, however, is still limited. 

After decontamination by emesis or lavage, patients should be carefully monitored for alterations in liver and kidney function, and treated symptomatically if necesseray. Seizures can be treated with anti-convulsant drugs. Because the toxin produces a deficiency of y-amino-butyric acid (GABA), specific treatment with pyridoxine (vitamin Bg) has been recommended. 

Mouse Bioassay. When administered at 5 mg per mouse in 0.5 ml dose during the initial screening, the WSAP from G. toxicus caused death in all test mice within 120 minutes. The toxin had a latency period of approximately 30 minutes after which signs of toxicity were noticeable, and included in order of occurrance inactivity and piloerection followed by cyanosis of the tail and feet with concurrent hypothermia, vasodilation in the ears ( scarlet ears ), lacrimation, ptosis of the eye lid on the side of injection, ptosis of the abdomen (loss of muscular tone), asthenia, impairment of hind limb motor ability followed shortly by complete paralysis with the hind limbs extended posteriorly (complete prostration), and dyspnea (respiratory distress). Death occurred without convulsions and the eyes became cataracted just prior to or after death. 

The aminopyridines (4-aminopyridine 3,4-diaminopyri-dine) accelerate spontaneous exocytosis at central and peripheral synapses. There is also an increase in the number of transmitter quanta released by a nerve action potential. This is probably the result of increased Ca++ inflow at the terminals due to a reduction of K+ conductance and prolongation of the nerve action potential. Muscle strength is increased in patients with the Lambert-Eaton myasthenic syndrome and in others poisoned with botuUnum E toxin (discussed later). Improvement in uncontrolled spasms, muscle tone, and pulmonary function is noted in patients with multiple sclerosis or long-standing spinal cord damage. Side effects that limit clinical utility include convulsions, restlessness, insomnia, and elevated blood pressure. Of the two agents, 3,4-diaminopyridine is the more potent and crosses the blood-brain barrier less readily. 

Some toxins in mushrooms are alkaloids that cause central nervous system effects of narcosis and convulsions. Hallucinations occur in subjects who have eaten mushrooms that contain psilocybin. The toxic alkaloid muscarine is present in some mushrooms. 

The structures of the penitrems were elucidated156 mainly by extensive n.m.r. studies, both on the natural material and on 13C-enriched material isolated after administration of appropriate 13C-labelled precursors (tryptophan and acetate) to the cultures. Structure (16a) incorporates the proposed relative stereochemistry of penitrem A, but no deductions concerning the stereochemistry of the other metabolites were made. Penitrem A is a powerful toxin, and causes sustained tremors, disco-ordination, and convulsions in laboratory and farm animals. 

Samandarine is a relatively potent, centrally active neurotoxin with an injected lethal dose for a mouse of about 70 jag (see Ref. 5, and references therein). Samandarone is somewhat less toxic. Convulsions, respiratory failure, cardiac arrhythmias, and partial paralysis precede death. The fire salamander is sensitive to its own toxin. 

Treatment involves sedating the patient and keeping them in a darkened room isolated from external stimuli. This is because the slightest noise or touch can be followed by a violent movement or convulsion. Sometimes an anaesthetic, such as ether or chloroform, was used to stop this reaction, but barbiturates seem more effective and are preferred. Helping the victim to survive the convulsions allows the body to metabolize and excrete the toxin. 

AH these toxins act in the same way nervous transmission is blocked when the PSP binds to site 1 of the sodium channels (CatteraU, 1980), and this induces muscle paralysis. In animals, typical neurological effects induced by this toxin include nervousness, jumping, jerking, ataxia, convulsions, and paralysis. The paralysis of respiratory muscles is fatal within a few minutes (Runnegar et al., 1988). Saxitoxins are toxic both by ingestion and by inhalation, and they could be dispersed as aerosols and inhaled, and so lead to rapid respiratory collapse and death. 

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