Catecholamines, structures

Noncatecholamine adrenomimetic drugs differ from the basic catecholamine structure primarily by having substitutions on their benzene ring. 

Most of the widely used antidepressants are tricyclics related to imipramine. A 1-phenyltetrahy-droisoquinoline analogue, nomifensine (60), departs from this structural pattern. Hiarmacologi-cally it inhibits the reuptake of catecholamines such as dopamine at neurons. It can be synthesized by alkylation of 2-nitrobenzyl-methylamine with phenacyl bromide followed by catalytic reduction of the nitro group (Pd-C) and then hydride reduction of the keto moiety to give 59. Strong acid treatment leads to cyclodehydration to nomifensine (60) [17]. 

Catecholamines are biogenic amines with a catechol (o-dihydroxy-benzol) structure. They are synthesized in nerve endings from tyrosine and include dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine). 

COMT O-methylates catecholamines and other compounds having a catechol structure including catecholoestrogens (Fig. 2). The two isoforms of... 

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

The phenylalkylamine hallucinogens show a close structural resemblance to the catecholamines, noradrenahne and dopamine. The prototype structure is found in mescaline, a naturally occurring substance. Modification of the mescaline molecule has led to synthetic amphetamine derivatives with hallucinogenic action. 

Bidwell LM, McManus ME, Gaedigk A, Kakuta Y, Negishi M, Pedersen L, et al. Crystal structure of human catecholamine sulfotransferase. / Mol Biol 1999 293 521-30. 

Buck K., Amara S. Chimeric dopamine-norepinephrine transporters delineate structural domains influencing selectivity for catecholamines and l-methyl-4-phenylpyridinium. Proc. Natl. Acad. Sci. U.S.A. 91 12584, 1994. 

Pericytes lie periendothelially on the abluminal side of the microvessels (Figure 15.3). A layer of basement membrane separates the pericytes from the endothelial cells and the astrocyte foot processes. Pericytes send out cell processes which penetrate the basement membrane and cover around 20-30% of the micro-vascular circumference [18]. Pericyte cytoplasmic projections encircling the endothelial cells provide both a vasodynamic capacity and structural support to the microvasculature. They bear receptors for vasoactive mediators such as catecholamines, endothelin-1, VIP, vasopressin and angiotensin II. Pericytes become mark-... 

Buck, K. J. and Amara, S. G. (1995) Structural domains of catecholamine transporter chimeras involved in selective inhibition by antidepressants and psychomotor stimulants. Mol. Pharmacol. 48,1030-1037. 

Some of these environmental aspects are obvious, such as anthropogenic sources of chemicals that disrupt the structure of delicate epithelia involved in solute transport, or directly inhibit the solute transporting proteins (e.g. Cu inhibition of Na+K+ ATPase [82]). The general effects of environmental stress are also well known, since many of the hormones released into the blood during stressful situations will alter the activity of ion transporters (e.g. corticosteroids, catecholamine [14]). 

Mercuric chloride may induce catecholamine release from adrenals. The initial phase may be due to amine displacement by the mercury ion but the secondary phase probably involves alteration of membrane structures [95]. Mercury compounds have also been shown to increase the efflux of monoamines from mouse striated slices [96] and from adrenergic nerve fibre terminals [97], the effect being attributed to inhibition of Na /K+-ATPase activity and(or) disruption of intracellular Ca2+ regulatory mechanisms [96]. 

Reductase in catecholamine-containing structures of rat, monkey brain by IHC (Haglund etal., 1984). 

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