Norepinephrine in CNS

These effects are produced mostly by phenylpropanolamines present in the leaves. These include cathinone [4] (5 -a-aminopropiophenone), cathine [5] [(-)-IS, 2S-norpseudoephedrine] and (-) -IR, 2S-norephedrine (8). These substances have pharmacological properties similar to those of amphetamine [6] (81), as they induce the release and inhibit the uptake of dopamine and norepinephrine in CNS (82). In addition to the known phenylpropylamines, the presence of other amines such as meracathine, pseudomeracathine and meracathinone have been identified (83, 84). Cathinone, being a ketoamine base, is extremely unstable and, in particular, it can be transformed into (+)-norpseudoephedrine and (-)-norephedrine by an enzymatic reduction. It can also be oxidized to give 1-phenyl-l,2-propandione, while the cathinone dimers, such as 3,6-dimethyl-2,5-diphenylpyrazine are purely artifacts of the isolation (85). 

Amitriptyline blocks reuptake of serotonin and norepinephrine in CNS. Chlordiazepoxide potentiates effects of GABA in CNS. The combination is indicated in the treatment of moderate to severe depression associated with moderate to severe anxiety. 

However, the exact problem in CNS amine neurotransmission remains a subject of much debate. One leading theory is that depression may be caused by an increased sensitivity of the presynaptic or postsynaptic receptors for these transmitters. That is, the neurochemistry of the brain has been changed in some way to make the amine receptors more sensitive to their respective amine neurotransmitters (norepinephrine, serotonin, and to a lesser extent, dopamine).21 This theory is based primarily on the finding that antidepressant drugs prolong the activity of amine neurotransmission in the brain, thereby causing a compensatory decrease in the sensitivity of the amine receptors.21,47... 

This effect is not surprising Amphetamines are potent psychomotor stimulants. Whether sniffed, swallowed, snorted, or injected, they induce feelings of power, strength, exhilaration, self-assertion, focus, and enhanced motivation. Amphetamine intake causes a release of the excitatory neurotransmitters dopamine and noradrenaline (norepinephrine) in the central nervous system (CNS). The release of dopamine typically induces a sense of aroused euphoria that may last several hours unlike cocaine, amphetamine is not readily broken down by the body. After taking amphetamines, feelings are intensified, the need to sleep or eat is diminished, and the user may feel as though he or she can take on the world. ... 

Although cocaine can function as a local anesthetic, most of its actions relate to a second mechanism. Cocaine increases synaptic concentrations of catecholamines (i.e., dopamine and norepinephrine) in the brain by blocking their reuptake mechanisms. Normally, when these transmitters are released from nerve terminals, they are rapidly removed from the synaptic cleft by specific energy-dependent transporter proteins that carry them back into the terminal. By blocking these transporter systems, cocaine prolongs the time the catecholamines remain in the synapse and intensifies their actions. This increase in dopamine concentration in the CNS appears to be the basis for the various euphoric and related changes that occur in people who use cocaine. A similar mechanism has been suggested for methamphetamine. 

Lithium s benefit in mania may be linked to effects on dopamine and norepinephrine, possibly by preventing dopamine receptor supersensitivity in the manic individual. Additionally, lithium blocks some cocaine- and amphetamine-induced symptoms of mania, which are thought to be mediated by stimulant-related increases in CNS dopamine concentration. The action of lithium on norepinephrine is variable, causing an initial prolonged increase in reuptake, although this effect is not evident with long-term administration (American Society of Hospital Pharmacists 1993). 

All psychostimulants appear to elevate synaptic levels of dopamine and norepinephrine. In addition, cocaine and, to a lesser extent, some of the other agents also raise synaptic levels of serotonin. It is the current consensus that elevated dopamine levels lead to CNS stimulation and are responsible for the reinforcing properties of stimulants (72-78). Nevertheless, recent studies have... 

Desipramine is a tricyclic antidepressant, inhibits reuptake of norepinephrine and serotonin in CNS, and is indicated in relief of symptoms of depression. Desipramine (75 to 150 mg p.o./day in divided doses) is indicated in endogenous depression major depression with melancholia or psychotic symptoms depression associated with organic brain disease, alcoholism, schizophrenia, or mental retardation and the depressive phase of manic-depressive disorder. Desipramine is absorbed rapidly from the GI tract, distributed widely in the body, and appears also in breast miUc. It is bound to plasma proteins to the extent of 90%, undergoes extensive first-pass metabolism, and its metabolites are excreted in urine. Desipramine strongly blocks the norepinephrine uptake mechanism and has no effect on the uptake of serotonin. Desipramine has weak alpha -adrenergic and... 

Isocarboxazid is an MAO inhibitor, which blocks activity of enzyme MAO, thereby increasing monoamine (e.g., epinephrine, norepinephrine, serotonin) concentrations in CNS. It is indicated in the treatment of depression. Isocarboxazid (30 mg/kg) is a monoamine oxidase inhibitor (MAO) indicated for the treatment of depressed patients who have become refractory to tricyclic antidepressants... 

Amoxapine is considered a heterocyclic drug even though it blocks the reuptake of norepinephrine in the CNS. 

Methylphenidate increases dopamine levels in the CNS, which then may be converted to norepinephrine in adrenergic terminals. This may result in mood elevation. The use of this drug, however, is limited to treatment-refractory cases or when standard medical therapies are nol tolerated, as CNS stimulants may aggravate coexisting anxiety or agitation in depressed patients. 

The vast majority of administered L-dopa is converted to dopamine (or norepinephrine) in peripheral neurons. Concurrent administration of a dopa decarboxylase inhibitor, such as carbidopa, decreases the peripheral conversion of the drug to dopamine (or norepinephrine) in a dose-dependent manner. Thus, the proportion of administered drug that enters the CNS is significantly increased, resulting in increased efficacy of L-dopa. Thus, concurrent administration of carbidopa allows for lower doses of L-dopa. 

Reserpine is sometimes used in the treatment of hypertension. In addition to depleting vesicular stores of norepinephrine in sympathetic nerve endings, reserpine depletes brain dopamine and causes parkinsonism-like adverse effects. Reserpine also decreases vesicular stores of norepinephrine and serotonin in CNS neurons, which can result in depression of mood. The answer is (E). 

Receptor interactions clonidine acts at postsyn-aptic alpha-2-adrenoreceptors in the CNS, mimicking the effects of norepinephrine to produce analgesia in animals and humans. Clonidine also stimulates release of the inhibitory neurotransmitters acetylcholine and norepinephrine in the dorsal horn. Stimulation of postsynaptic alpha-2-adrenoceptors in the brainstem and sympathetic preganglionic neurons in the spinal cord decreases sympathetic outflow, causing hypotension and bradycardia depending on the extent of spread. Alpha-2-adrenergic activity in the... 

Two studies report on the interaction of A -THC with anesthetics. The minimum alveolar anesthetic (MAC) requirements for cyclopropane in rats and halothane in dogs were significantly decreased by pretreatment with A -THC. Analgesia, sedation and prolonged barbiturate sleeping time after acute A -THC injection may reflect the potential additive anes-thetic-like action of the drug. Alternatively, drvigs that deplete norepinephrine in the CNS decrease halothane MAC . 

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