Norepinephrine, biological effects

Norbolethone, 151 Norepinephrine, biological effects, 38 Norethindrone, 145 Norgestrel, 151 19-Nortestosterone, 142 Nucleophilic aromatic substitution, 64, 65,... 

The adrenal medulla synthesizes two catecholamine hormones, adrenaline (epinephrine) and noradrenaline (norepinephrine) (Figure 1.8). The ultimate biosynthetic precursor of both is the amino acid tyrosine. Subsequent to their synthesis, these hormones are stored in intracellular vesicles, and are released via exocytosis upon stimulation of the producer cells by neurons of the sympathetic nervous system. The catecholamine hormones induce their characteristic biological effects by binding to one of two classes of receptors, the a- and )S-adrenergic receptors. These receptors respond differently (often oppositely) to the catecholamines. 

The biological effects of epinephrine and norepinephrine are mediated by nine different adrenoceptors (a1A,B,D, a2A,B,c. Pi, P2. P3)-To date, only the classification into a-i, a2, pi and p2 receptors has therapeutic relevance. 

The first molecules identified as transmitters of information within both the peripheral nervous system (PNS) and brain (CNS) were acetylcholine (ACh), norepinephrine (NE), and 5-HT. ACh is the neurotransmitter in the autonomic nervous system Profound biological effects can result from even shght changes of molecular configuration. 

In 1817, die Swede Johann Arfvedson discovered the element lithium. Its biological effect is on intracellular influx of sodium during the process of axonal depolarization, which interferes with the synthesis and reuptake of neurotransmitters. In the 1950s, it began to be used in the treatment of bipolar disorder, because it dampens neurotransmission. It enhances the reuptake of dopamine, norepinephrine, and 5-HT into neuronal vesicles, reducing their action. It also reduces release of norepinephrine from synaptic vesicles and inhibits production of cAMP. It decreases the neuronal activity excited by 5-HT, dopamine, and epinephrine. 

Adrenergic drugs are natural or synthetic compounds that either partially or completely replicate the effects of norepinephrine (noradrenaline), epinephrine (adrenaline), and dopamine, and which cause a biological response similar to the activation of the sympathetic nervous system. They are also referred to as sympathomimeties beeause they mimic the stimulation of the sympathetic nervous system. 

ADRENAL MEDULLA HORMONES. Adrenaline (epinephrine) and its immediate biological precursor noradrenaline (norepinephrine, levartei-nol) are the principal hormones of the adult adrenal medulla. See Fig.l. Some of the physiological effects produced by adrenaline arc contraction of the dilator muscle of the pupil of the eye (mydriasis), relaxation of the smooth muscle of the bronchi constriction of most small blood vessels dilation of some blood vessels, notably those in skeletal muscle increase in heart rate and force of ventricular conlraction relaxation of the smooth muscle of the intestinal tract and either contraction or relaxation, or both, of uterine smooth muscle. Electrical stimulation of appropriate sympathetic (adrenergic) nerves can produce all the aforementioned effects with exception of vasodilation in skeletal muscle. 

Levodopa (L-dopa) is a natural intermediate in the biosynthesis of catecholamines in the brain and peripheral adrenergic nerve terminals. In the biologic sequence of events it is converted to dopamine, which in turn serves as a substrate of the neurotransmitter norepinephrine. Levodopa is used successfully in the treatment of Parkinson s syndrome, a disease characterized by dopamine deficiency. When levodopa is administered to an individual with this syndrome, the symptoms of Parkinson s disease are ameliorated, presumably because the drug is converted to dopamine and thereby counteracts the deficiency. Individuals treated with levodopa, especially older men, have been observed to experience a sexual rejuvenation. This effect has led to the belief that levodopa stimulates sexual powers. Consequently, studies with younger men complaining of decreased erectile ability have shown that levodopa increases libido and the incidence of penile erections. Overall, however, these effects are short lived and do not reflect continued satisfactory sexual function and potency. Thus, levodopa is not a true aphrodisiac. The increased sexual activity experienced by parkinsonian patients treated with levodopa may reflect improved well-being and partial recovery of normal sexual functions that were impaired by Parkinson s disease. 

MAO inhibitors were the first widely used antidepressants, but because of various undesirable side effects they are employed today in only a more limited number of cases. People who are treated with MAO inhibitors, for example, must be careful of their diet. They should not eat food rich in tyramine or other biologically active amines. These foods include cheese, beer, and red wine. Individuals on MAO inhibitors are unable to inactivate tyramine present in the food. Because tyramine causes the release of endogenous norepinephrine, patients are susceptible to increased blood pressure (e.g., potential lethal cerebral hemorrhages) and cardiac arrhythmias. 

Monoamine oxidase, which exists in two distinct forms, referred to as MAO A and MAO B, is one of the enzymes responsible for the degradation of biologically important amines. Compounds that block the catalytic action of MAO A, which is selective for the degradation of norepinephrine and serotinin, have antidepressant effects whereas compounds that inhibit MAO B, which degrades dopamine in the brain, are useful for treating Parkinson s disease [190, 191]. Both MAO A and MAO B contain flavin co-enzyme attached at the 8-a-position to an enzyme-active cysteine residue (54). A one-electron transfer mechanism (Scheme 15) for the oxidations catalyzed by MAO was first proposed by Silverman [192] and Krantz [193,194]. 

Use of lithium is based in the biological theory that bipolar disorder results from an overactivity of the neurotransmitters in the brain. Lithium appears to enhance reuptake of serotonin and norepinephrine at the presynaptic level and to decrease dopamine and norepinephrine effects at the postsynaptic receptors. 

Colucci WS. The effects of norepinephrine on myocardial biology Implications for tiie tiier y of heart failure. Clin Cardiol 1998 21 120-24. 

If the tertiary pr-MDI and bu-MDI gain access to the interior of the cell to exert their calcium antagonistic actions, it would be predicted that their quaternary ammonium analogues would be inactive due to their exclusion from the intracellular compartment as a result of their inability to cross biological membranes. As predicted, the tertiary, but not the quaternary, MDIs produce a negative inotropic effect on the isolated electrically-driven guinea pig left atrium (42) and inhibit potassium-induced and norepinephrine-induced contractions of the isolated rat aortic strip (43). 

Hormones have several important functions in the body. They help maintain homeostasis, the balance of biological activities in the body. The effect of insulin in keeping the blood glucose level within narrow limits is an example of this function. The operation of epinephrine and norepinephrine in the fight-or-flight response is an example of the way in which hormones mediate responses to external stimuli. Finally, hormones play roles in growth and... 

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