Norepinephrine chemistry

Figure 2 Selective electrochemical detection of a mixture on multielectrode amper-ometry. AA = Ascorbic acid, NE = norepinephrine, DOPAC = 3-4-dihydroxy-phenylacetic acid, E = epinephrine bitartrate, 5-HIAA = 5-hydroxyindole-3-acetic acid, HVA = homovanillic acid, TRP = tryptophan, 5-HT = 5-hydroxytryptamine, and 3-MT = 3-methoxytyramine (separated by RPLC). Detection was with a 4-electrode glassy carbon array, with electrode 1 at 500 m V) electrode 2 at 700 mV, electrode 3 at 900 mV, and electrode 4 at 1100 mV. Note that at electrode 1, HVA, TRP, and 3-MT are not seen. At electrode 2, only TRP is not seen. A standard calomel electrode was used as reference. (Reprinted with permission from Hoogvliet, J. C., Reijn, J. M., and van Bennekom, W. P., Anal. Chem., 63, 2418, 1991. 1991 Analytical Chemistry.)...

Jawless fish (Cambrian) As above second hydroxylation giving norepinephrine and amidated peptides copper chemistry in vesicles Recovery additionally by hydrolysis Zinc enzymes... 

MAO A and B differ in primary structure and in substrate specificity [5,7]. The two isozymes, located on the mitochondrial outer membranes, have 70% homology in peptide sequence and share common mechanistic details. It is now recognized that these are different proteins encoded by different genes, but probably derived from a common ancestral gene. Crystal structures for both MAO A and B complexes with inhibitors have recently been reported [8]. Serotonin is selectively oxidized by MAO A, whereas benzylamine and 2-phenylethylamine are selective substrates for MAO B. Dopamine, norepinephrine, epinephrine, trypt-amine, and tyramine are oxidized by both MAO A and B in most species [9]. In addition, MAO A is more sensitive to inhibition by clorgyline (1), whereas MAO B is inhibited by low concentrations of L-deprenyl ((f )-( )-deprenyl) (2) [5,6cj. Development of inhibitors that are selective for each isozyme has been an extremely active area of medicinal chemistry [8]. 

Cocaine [50-36-2] - [ALKALOIDS] (Vol 1) - [ALKALOIDS] (Vol 1) -and catecholamines [EPINEPHRINE AND NOREPINEPHRINE] (Vol 9) -forensic testing for [FORENSIC CHEMISTRY] (Vol 11) -substance abuse of [PSYCHOPHARMACOLOGICAL AGENTS] (Vol 20)... 

The active ingredient of St. John s wort is a substance called hyperforin. Like other antidepressants, hyperforin appears to work by helping to restore the proper balance to brain chemistry. In particular, hyperforin helps restore the balance of certain neurotransmitters, or chemical messengers, in the brain. These neurotransmitters include serotonin, norepinephrine, and dopamine. 

In several papers the Kunos group has reported observations that may represent a starting point for novel medicinal chemistry research in this area [167, 168], Anandamide (i.v. bolus 4 mg/kg) caused a triphasic blood pressure response, brief hypotension, followed by a transient pressor and then a prolonged depressor phase. The hypotensive effect was not initiated in the CNS, but was due to a presynaptic action that inhibited norepinephrine release from sympathetic nerve terminals in the periphery (heart and vasculature). The inhibitory effect (but not the pressor effect) was antagonized by SR141716A, indicating that this peripheral action was mediated by CB receptors. 

The naturally occurring catecholamines dopamine (1), norepinephrine (2), and epinephrine(3) (Figure 1) play key roles in neurotransmission, metabolism, and in the control of various physiological processes. For example, norepinephrine is the primary neurotransmitter in the sympathetic nervous system and also functions as a neurotransmitter in the central nervous system. Epinephrine, elaborated by the adrenal gland, has potent effects on the heart, vascular and other smooth muscles. Dopamine is an important neurotransmitter in the central nervous system, and has important peripheral effects in such organs as the kidney and heart. The importance of these effects has made the search for drugs that can mimic, inhibit, or otherwise modulate the effects of these catecholamines an important area of medicinal chemistry. 

Current theories regarding the causes of depression support the role of the neurotransmitters serotonin (also known as 5-HT) and norepinephrine (NE) in depression and their interrelationships with each other and with dopamine (Fig. 21.1). Although the precise nature of the depression is not fully understood at the level of the chemistry in the brain, several theories explain the role of NE and 5-HT in the causes of depression (7). 

Back to the commentary on BOD. The rationale for this inclusion of a beta-oxygen atom into the structure of a phenethylamine is based directly on the chemistry that occurs naturally in the brain. The phenethylamine neurotransmitter, dopamine, is converted both in the brain and in the body to the equally important transmitter norepinephrine by just this sort of transformation. 

The importance and versatility of the Friedel-Crafts reaction in thiophene chemistry can be seen in the following examples of duloxetine synthesis involving Friedel-Crafts acylations. Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) known for its use as an antidepressant. 

Arnett, C.D., Wright, (., and Zenker, N. (1978) Synthesis and adrenergic activity of benzimidazole bioisosteres of norepinephrine and isoproterenol. Journal of Medicinal Chemistry, 21 (1), 72-78. 

---