Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

MAGNESIUM GLUTAMATE HYDROBROMIDE

NFPA

PRODUCT USE

Sedative and hypnotic in the treatment of insomnia, neuroses and behavioural disorders.

SYNONYMS

C5-H7-N-O4.Br-H.Mg, C5-H7-N-O4.Br-H.Mg, (C5H8NO4)2Mg.HBr, "L-glutamic acid, magnesium
salt (1:1), hydrobromide", "L-glutamic acid, magnesium salt (1:1), hydrobromide",
"magnesium bromoglutamate", "magnesium alpha-aminoglutarate hydrobromide", Bromolate,
Hyposed, Psicosoma, Psycho-Soma, Psycho-Verlan, "sedative/ hypnotic"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

None

EMERGENCY OVERVIEW

RISK

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Although ingestion is not thought to produce harmful effects, the material may still be damaging to the health of the individual following ingestion, especially where pre-  existing organ (e.g. liver, kidney) damage is evident. Present definitions of harmful or toxic substances are generally based on doses producing mortality (death) rather than those producing morbidity (disease, ill-health). Gastrointestinal tract discomfort may produce nausea and vomiting. In an occupational setting however, ingestion of insignificant quantities is not thought to be cause for concern.  Magnesium salts are generally absorbed so slowly that oral administration causes few toxic effects, as the dose is readily expelled via the bowel. If evacuation fails, mucosal irritation and absorption may result. This can result in nervous system depression, heart effects, loss of reflexes and death due to paralysis of breathing. These usually do not occur unless the bowel or kidneys are damaged.  Bromide poisoning causes intense vomiting so the dose is often removed. Effects include drowsiness, irritability, inco-ordination, vertigo, confusion, mania, hallucinations and coma. Other effects include skin rash, nervous system symptoms, sensory disturbances and increased spinal fluid pressure. They have been used as sedatives and depress the central nervous system. Toxicity is increased if dietary chloride is reduced. Repeated ingestion can cause a syndrome with acne, confusion, irritability, tremor, memory loss, weight loss,  headache, slurred speech, delusions, stupor, psychosis and coma.  Persons exposed to this material at work are liable to the same side effects as those taking this material in supervised conditions. Persons with a psychiatric history taking drugs should be monitored carefully as they are more prone to dependence and addiction. Side effects of sleeping medication include drowsiness, dizziness, light-headedness and inco-ordination and alcohol can increase them. Drug dependency can occur after a few weeks of nightly administration. Withdrawal of the drug is associated with a range of unpleasant effects and severity; it can also cause rebound insomnia where the symptoms are worse than before. Rarely, behavior changes may follow administration of sleeping drugs. If used late in pregnancy it can sedate the fetus.  The material may bind to the N-methyl-D-aspartate (NMDA) neuroreceptor. The NMDA receptor is an ionotropic glutamate receptor found on post-synaptic neurons and is a membrane channel that regulates the flow of sodium and calcium ions, flowing into the neuron, while potassium ions flow out. The NMDA receptor, therefore, tightly regulates "ion channel conductance". NMDA agonists (receptor activators), such as the glutamates, can, however, be highly toxic to the neuron. Excessive amounts of glutamate or its congeners, can be highly toxic to neurons and may contribute to neuron damage/death in stroke, epilepsy and neurodegenerative diseases. The decreased supply of oxygen (hypoxia) in stroke has been shown to result in excess glutamate release.Overactivation by glutamates, other excitatory amino-acids (EAAs) such as the cysteines and homocysteines, and its congeners (excitotoxins), causes an excessive influx of calcium, into neurons, triggering nervous tissue damage. Glutamate is the major excitatory neurotransmitter in the central nervous system. When concentrations of glutamate and excitotoxins rise above a certain level, in the extracellular fluid, the neuron begins to fire abnormally. At higher concentrations, the cells of the neuron undergo a specialised process of delayed cell death known as excitotoxicity. Although the effects of excitotoxins are generally not dramatic, certain individuals may be especially sensitive and may develop severe symptoms as a result of cardiac irritability.Excess calcium can activate pathways that are potentially harmful to the cell. For example, kinases, phospholipase A2, calpains, NO synthase, endonucleases and other enzymes can be activated. Phospholipase A2 stimulates arachidonic acid production while NO synthase produces nitric oxide. The production of both species ultimately results in free radical damage. Calpain activation may cause breakdown of the cytoskeleton and also contributes to free radical production and lipid peroxidation. Endonucleases damage neuronal DNA, as do free radicals. In addition, high internal calcium ion concentrations create large osmotic forces that drive water into the cell causing swelling and possibly, rupture. Rupture, in turn, causes the release of even more glutamate, inducing excitotoxicity in neighbouring cells. When brain cells are injured, they also release large amounts of glutamate from surrounding astrocytes and this glutamate can produce further damage in adjacent normal neuronal cells. This appears to be the case in strokes, seizures and brain trauma.Activation of calcium-dependent enzymes is thought to produce changes in neuronal function that are long-lasting, persisting for weeks or months; it has been suggested that such activation is responsible for memory. Blockade (antagonism) of the receptor by several chemical agents produces amnesia in laboratory animals.NMDA antagonists have been used as neuroprotective agents counteracting the effects of overactivation of the receptor; however such antagonists may also be harmful, at high doses, as the neuron also needs calcium for normal function. Very high doses may produce irreversible damage (including the psychomimetic effects caused by PCP -"angel dust"- abuse). Certain NMDA antagonists (notably those used to produce anaesthesis) induce arousal and even seizures. This class of drug has also produced a model psychosis indistinguishable from schizophrenia.Large doses of calcium channel blocking agents may produce nausea, weakness, dizziness, drowsiness, confusion and slurred speech. Marked and prolonged hypotension and bradycardia may result from second or third degree atrioventricular block, decreased cardiac output and junctional rhythms; death may ensue.Certain NMDA receptor antagonists may produce lightheadedness, ataxia, mood elevation and muscle incoordination. Side-effects of uptake of these antagonists (such as the isoxazole derivative, ibotenic acid, isolated from hallucinogenic mushrooms), by neurones, include dizziness, ataxia, euphoria, muscle twitches, and initial psychic stimulations followed by dream-filled sleep. More severe ingestions may produce visual disturbances, fever, confusion, myoclonus, mydriasis, seizures and coma. Residual headache may persist for several days. Ibotenic acid binds to NMDA neurotransmitter and inhibits (antagonises) its action. The congener muscimol (also isolated from mushrooms) which is structurally related to ibotenic acid and glutamic acid,  by contrast, binds to another neuroreceptor, the so-called GABA receptor. This receptor, when activated inhibits the firing of some central neurones by causing influx of anions (e.g. chloride) into the cell. Muscimol is a GABA receptor agonist and produces a similar effect and almost identical clinical outcome to that of ibotenic acid. Systemic administration of ibotenic acid and muscimol to laboratory animals produces central inhibition of motor activity with little change to peripheral autonomic activity. Both compounds induce EEG changes in cats, rabbits and rats and thus within the central nervous system both compounds behave as false inhibitory neurotransmitters.There are at least five different NMDA receptor sites that determine whether or not the channel opens. Two important ligands, glutamate and glycine (both amino-acids), are required to bind their respective NMDA sites for the channel to open. At low micromolar concentrations, polyamines, such as dopamine or cholinergic agents (binding to polyamine sites), increase the probability that glutamate and glycine will open the channel; high concentrations of polyamine, in contrast, produce the reverse effect. Two other regulatory ions, magnesium and zinc inhibit the action of amino- acids by binding to sites in the inner pore region of the NMDA channel.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may produce transient discomfort characterized by tearing or conjunctival redness (as with windburn).  

SKIN

  The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Solution of material in moisture on the skin, or perspiration, mayincrease irritant effects.  

INHALED

  Inhalation may produce health damage*.  The material is not thought to produce respiratory irritation (as classified using animal models). Nevertheless inhalation of the material, especially for prolonged periods, may produce respiratory discomfort and occasionally, distress.  Not normally a hazard due to non-volatile nature of product.  Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.  

CHRONIC HEALTH EFFECTS

  Principal routes of exposure are by accidental skin and eye contact andinhalation of generated dusts.  Babies born to mothers taking sedatives/hypnotics may show withdrawal symptoms from the drug in the weeks after birth. Loss of muscle tone in these babies has also been noted.