Catecholamine release, suppression

The cocaine- and amphetamine-regulated transcript receptor is involved in the action of CART as a leptin-induced, hypothalamic anorexigenic (appetite-suppressing) hormone, CNS stimulant and inducer of catecholamine release from presynaptic storage granules. 

Cyanide also causes endogenous catecholamine release (Kanthasamyeta/., 1991 Kawada eta/., 2000 Schomiget a/., 1995 Inoue et al, 1998). Inoue et al (1998) also point out that cyanide-produced depolarization increases intracellular calcium due to the suppression of the potassium channels and activation of the voltage-dependent calcium channel. Anoxia induces suppression of the sodium pump and activates cation channels due to the decrease in ATP. A further consequence of the presence of cyanide in the tissue is inhibition of the Na+/Ca + exchanger (NCX) (Ju and Allen, 2005). NCX is important for the pacemaker currents. Metabolic inhibition of NCX reduces the firing rate of pacemaker cells. 

Principle Clonidine activates Oj-adrenergic receptors in the brain and sympathetic nerve endings to suppress norepinephrine release by sympathetic nerves without effect on catecholamine release from pheochromocytomas. 

Amphetamine has several important central actions, it causes a well-known central excitation accompanied by increased motor activity, it also has temperature-elevating and appetite-suppressing actions. This amine is classified as an indirectly acting sympathomimetic in peripheral adrenergic systems, and there is considerable evidence that it may act centrally by displacing NA and/or DA. The main evidence in favour of this view is that the locomotor stimulating actions of amphetamine are blocked in animals pretreated with inhibitors of catecholamine biosynthesis, such as a-methyl-p-Tyr. On the other hand, the central actions of amphetamine are not markedly reduced, and may even be enhanced, in reserpine-treated animals, in which the central catecholamine stores are severely depleted. However, even in reserpinized animals, a small pool of newly synthesized NA may still be available for release by amphetamine. In addition to the possibility of catecholamine release, amphetamine also has other actions on central adrenergic neurons. It is an inhibitor of MAO, and a potent inhibitor of both the NA and DA uptake processes. 

Phentermine (Adipex-P) b b 3.2 (0.1) An anorexiant that suppresses appetite by acting on the hypothalamus, leading to an increased release of catecholamines, ultimately reducing the appetite. 

Mechanism of Action An amphetamine that enhances the action of dopamine and norepinephrine by blocking their reuptake from synapses also inhibits monoamine oxidase and facilitates the release of catecholamines. Therapeutic Effect Increases motor activity and mental alertness decreases motor restlessness, drowsiness, and fatigue suppresses appetite. 

Some information is available on the relationship between the CCK and the noradrenergic systems. In the lateral hypothalamus of satiated rats, perfused CCK-8S by push-pull perfusion enhanced the efflux of noradrenaline. However, in fasted animals, CCK-8S often suppressed the catecholamine s release. Perfused in the lateral hypothalamus, CCK exerted opposite effects. 

Methenamine mandelate, 1 g four times daily, or methen-amine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4-12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites. 

Neuropeptide Y (NPY) suppresses the pacemaker current If. Colocalized with norepinephrine in sympathetic nerve terminals on the heart, it is released with catecholamines dming sympathetic neural activation. NPYs on car-diomyocytes have surface membrane binding sites and... 

In a related vein, the subjective psychostimulant effects of amphetamine were attenuated following a 2-h pretreatment with a tyrosine- and phenylalanine-free amino acid mixture (118).These amino acids are biosynthetic precursors of the catecholamines, and deprivation would be expected to produce transient reductions in endogenous dopamine and norepinephrine. The authors concluded that tyrosine depletion attenuates the release of dopamine required for the psychostimulant effect. Interestingly, the pretreatment did not reduce the subjective appetite-suppressant (anorectic) effect of amphetamine. The study authors attributed this latter finding to a continued release of norepinephrine by amphetamine. Tyrosine depletion, however, would also attenuate norepinephrine biosynthesis and it may be more reasonable to conclude that the anorectic effect might be related to the often-overlooked ability of amphetamine to release neuronal serotonin. 

ANG II is also known to induce release of catecholamines from the adrenal medulla and to suppress the reflex inhibition of the heart rate, with the latter probably the inhibiting vagal (cholinergic) neurons to the heart. This has a specific clinical effect that is useful in the use of ACE inhibitors as antihypertensives (see later) namely, the absence of reflex tachycardia seen with other types of blood pressure-lowering drugs such as a-blockers, diazoxide, hydralazine, and ganglionic blockers. 

In recent times, no other group of substances has featured more frequently or more intensively in the media than the amphetamines, the so-called designer drug ecstasy being in the forefront of these reports. A common feature of these substances is their stimulation of the central nervous system, which depends on the release of catecholamines. Therapeutically, substances of this group are used as appetite suppressants, antihypotonics and psychoanaleptics. They can be divided into five groups ... 

Nevertheless, phentermine, from SmithKUneBeecham, became the first appetite suppressant (anorectic), which was approved by the FDA in 1959 (Fig. 5.106). [243] Phentermine leads to increased release of catecholamines like dopamine, adrenaline (epinephrine) and noradrenaline (norepinephrine), which reduce the sensation of hunger. However, the effect declines in the course of several weeks. Due to grave side-effects (sleeplessness, nervousness, nausea, obstipation. Angina pectoris problems and acute psychoses) the drug has meanwhile been withdrawn from a number of markets. 

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