Sympathomimetic synapse

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Cocaine is a local anesthetic with a peripheral sympathomimetic action that results from inhibition of transmitter reuptake at noradrenergic synapses (see Chapter 6 Introduction to Autonomic Pharmacology). It readily enters the central nervous system and produces an amphetamine-like effect that is shorter lasting and more intense. The major action of cocaine in the central nervous system is to inhibit dopamine reuptake into neurons in the "pleasure centers" of the brain. These properties and the fact that it can be smoked, "snorted" into the nose, or injected for rapid onset of... 

The effects of amphetamines are due to the increase of neurotransmitters norepinephrine, serotonin, and dopamine in central synapses. This increase is from increased release and reuptake blockade of catecholamines. Amphetamines may also inhibit monoamine oxidase. These mechanisms combine to produce the sympathomimetic and central nervous system (CNS) effects seen with amphetamine abuse. 

Cocaine is a potent CNS stimulant that elicits a state of increased alertness and euphoria with its actions similar to those of amphetamine but of shorter duration. These CNS effects are thought to be largely associated with the ability of cocaine to block dopamine reuptake at nerve synapses and thereby prolong the action of dopamine in the CNS. It is this response that leads to recreational abuse of cocaine. Cocaine also blocks the reuptake of norepinephrine at presynaptic nerve terminals this produces a sympathomimetic response (including an increase in blood pressure, heart rate, and body temperature). Cocaine is effective as a local anesthetic and vasoconstrictor of mucous membranes and is therefore used clinically for nasal surgery, rhinoplasty, and emergency nasotracheal intubation. 

Mode of action Sympathomimetic agonists may directly activate their adrenoceptors, or they may act indirectly to increase the concentration of catecholamine transmitter in the synapse. Amphetamine derivatives and tyramine cause the release of stored catecholamines these sympathomimetics are therefore mainly indirect in their mode of action. Another form of indirect action is seen with cocaine and the tricyclic antidepressants these drugs inhibit reupmke of catecholamines by nerve terminals and thus increase the synaptic activity of released transmitter. 

The hormones are stored in special granules which are present in the sympathetic nerve endings and medullary cells and the net hormonal output depends on the rates of both the synthesis and release. Any catecholamine that diffuses from the synapse into the remainder of the neuron is destroyed by a monoamine oxidase. Sympathomimetic drugs such as ephedrine and the amphetamines act by inhibiting monoamine oxidase and slowing the removal of catecholamines and 5-hydroxytryptamine (serotonin) from within neurons. In this way they increase the sensitivity of the neuron to stimulation and act as antidepressants. Any catecholamines that are released into the bloodstream are rapidly removed and inactivated by the liver. 

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