Uptake of catecholamines

Koe B. Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J. Pharmacol. Exp. Ther. 199 649, 1976. 

G.B. Baker, H.R. McKim, D.G. Caiveriey, W.G. Dewhurst, Effects of the monoamine oxidase inhibitors tranylcypromine, phenelzine and pheniprazine on the uptake of catecholamines in slices from rat brain regions, Proc. Eur. Soc. Neurochem. 1 (1978) 536. 

Wong DT, Bymaster FP Effect of nisoxetine on uptake of catecholamines in synaptosomes isolated from discrete regions of rat brain. Biochem Pharmacol 25 1979-1983, 1976... 

The mechanisms by which 2-PAM exerts its cardiac effects have been studied in experimental animals. At least three classes of action have been attributed to the effects of altered calcium metabolism on autonomic ganglia. A sympathomimetic action of 2-PAM was postulated to explain the increase in blood pressure and the augmented myocardial contractility by one or more of the following mechanisms 2-PAM may not block the release of the endogenous compounds, but may prevent the uptake of catecholamine 1 it may stimulate the release of norepinephrine it Increases myocardial contractility by directly stimulating beta receptors and it increases blood pressure by directly stimulating alpha receptors. 5... 

Sympathomimetic effects (from NA re-uptake inhibition) and antimuscarinic effects can cause a sinus tachycardia. Postural hypotension may occur as a result of sympatholytic al-adrenoceptor antagonism. With overdoses of these drugs, there is a reduced re-uptake of catecholamines, resulting in arrhythmias and hypertension. Tricyclic compounds have a high... 

Cocaine, which blocks the uptake of catecholamines, produces dose-dependent effects, initially causing euphoria, vasoconstriction, and tachycardia, and in toxic doses, convulsions, myocardial depression, ventricular fibrillation, medullary depression, and death. Cocaine is able to block nerve conduction and currently is used only for topical anesthesia. 

Cocaine is a powerful CNS stimulant as well as local anesthetic (13). It is isolated from the leaves of Erythrolon coca, a tree indigenous to Peru and Bolivia. Cocaine effectively blocks the uptake of catecholamines into presynaptic neurons and thus promotes the activity of synapses (both central and peripheral) involving these amines (22). 

Miles PR, Mundorf ML, Wightman RM. Release and uptake of catecholamines in the bed nucleus of the stria terminalis measured in the mouse brain slice. Synapse. 2002 44 188-197. 

Cocaine (alkaloid) is used medicinally solely as a surface anaesthetic (for abuse toxicity, see p. 192) usually as a 4% solution, because adverse effects are both common and dangerous when it is injected. Even as a surface anaesthetic sufficient absorption may take place to cause serious adverse effects and cases continue to be reported only specialists should use it and the dose must be checked and restricted. Cocaine prevents the uptake of catecholamines [adrenaline (epinephrine), noradrenaline (norepinephrine)] into S5nnpathetic nerve endings, thus increasing their concentration at receptor sites, so that cocaine has a built-in vasoconstrictor action, which is why it retains a (declining) place as a... 

Tricyclic antidepressants inhibit the uptake of catecholamines, such as adrenaline, into sympathetic neurons and can enhance the cardiovascular effects, so that even the small amounts of adrenaline present as additives in some local anesthetics can have a marked effect on the cardiovascular system. 

Tricyclic antidepressants inhibit the uptake of catecholamines, such as ephedrine, into sympathetic neurons and can enhance their cardiovascular effects (41). 

Assay of ATP-dependent uptake of catecholamines or amino acid transmitters... 

Miscellaneous antirheumatic drugs and their possible modes of action, 11. 1 Molecular aspects of the storage and uptake of catecholamines. 6. 121 Molecular mechanisms of specificity in DNA-antitumour drug interactions, 18, 1 Molecular pharmacology and therapeutic potential of thromboxane A receptor antagonists. 

NET-KO mice were used to demonstrate heterologous uptake of catecholamines in certain brain areas. Particularly, in the frontal cortex synaptosomes from NET-KO mice, no inhibitory effect of cocaine and nisoxetine on uptake of DA was found, whereas effectiveness of cocaine in the nucleus accumbens was somewhat reduced (16). Thus, it has been demonstrated that DA uptake in brain regions with low levels of the DAT may occur via NET (16). Similar conclusions were reached recently when voltammetric analyses of catecholamine clearance in the frontal cortex (97) and bed nucleus of the stria terminalis (98) were performed. 

Prazosin, terazosin, and doxazosin are selective aj -receptor blockers. They work in the peripheral vasculature and inhibit the uptake of catecholamines in smooth muscle cells, resulting in vasodilation and BP lowering. 

Cocaine is a central nervous system stimulant that inhibits the peripheral re-uptake of catecholamines, leading to increased sympathomimetic activity [115]. Its abuse is associated with a variety of medical problems. These include acute myocardial infarction, cardiac arrhythmias, cerebrovascular accidents, hyperpyrexia and stimulated sympathetic activity, seizures and coma, obstetrical complications, intestinal ischemia, and a variety of psychiatric complications [114-117]. The most prominent renal complication of cocaine abuse is acute renal failure associated with rhabdomy-olysis. 

I. Mechanism of toxicity. The primary actions of cocaine ate local anesthetic effects (see p 74), CNS stimulation, and inhibition of neuronal uptake of catecholamines. 

Other recent reports which indirectly tend to weaken the concept that norepinephrine is the sole alerting neurohumor indicate that (1) imipramine hyperactivity may result from blocking uptake and reducing nervous impulse flow in central serotonin neurons (2) drugs which Inhibit uptake of catecholamines also block serotonin accumulation in rabbit brain stem preparations (3) the increase in overt stimulation caused by 5-hydroxy-tryptophan may be associated with Impaired norepinephrine synthesis rather than increased norepinephrine release and (4) norepinephrine and dopamine inhibit electrical activity of central neurons as determined microelectro-phoretically although another study indicated that norepinephrine does cause neuronal excitation ... 

Since both MAO and COMT are intracellular enzymes, extracellular catecholamines must enter cells before catabolism can occur. This may involve a mediated transport of the catecholamines across the cell-membrane (Para. S.2.8). Certain drugs which block the formation of catecholamine metabolites, without themselves being inhibitors of either MAO or COMT, may act by blocking the uptake of catecholamines into such sites of catabolism (e.g. phenoxybenzamine). 

Table 11. Species Differences in the Uptake of Catecholamines BY Perfused Hearts...

Comparable lack of specificity plagues known methods of depleting 5-HT from brain reserpine and similar amine-releasing drugs block the intraneuronal vesicular uptake of catecholamines as well as of 5-HT. Lesions in the nucleus Raphd, the medial forebraln bundle and other tracts,5 which deplete 5-HT from brain, deplete NE as well. Prolonged Trp deficient dlets cause general nutritional deficits and an inefficient decrease in 5-HT levels. Substituted phenethylamine derivatives, such as p-chloromethamphetamine and fenfluramine, have usually been reported to exert relatively small effects on brain 5-HT and the mechanism... 

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