Reserpine Adrenaline

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

Metirosine (a-methyl-p-t5n osine) is a competitive inhibitor of the eruyme tyrosine hydroxylase, which converts t5U-osine to dopa as dopa is further converted to noradrenaline and adrenaline they are similarly depleted by metirosine. It is used as an adjuvant (with phenoxybenzamine) to treat phaeo-chromocytomas that caimot be removed surgically. Catecholamine synthesis is reduced by up to 80% over 3 days. It also readily penetrates the CNS and depletes brain noradrenaline and dopamine causing reserpine-like side effects (see above). Hence, in patients whose life expectancy is threatened more by tumour invasion than by mild or moderate hypertension, the need for the drug should be weighed carefully. 

Epinephrine (adrenaline) was one of the first hormones for which differential effects on blood pressure were reported for the two epimers in the early 20th century [58]. A reassessment of epinephrine activity was made by analyzing the effects of optical isomers of ephedrine and methylephedrine on the spontaneous beating rate of the isolated right atrium of normal and reserpinized rats by investigating direct and indirect actions on al-adrenoceptors. L-ephedrine, and to a lesser extent D-ephedrine, markedly increased the beating rate of rat right atrium [59]. 

Uptake blocker (Table 12) display a certain degree of structural relatedness to the endogenous neurotransmitter whose transport is inhibited dopamine uptake by the anonaine, cocaine, ibogaine, and salsolinol (see Scheme II) serotonin by 12-hydroxyibogaine, ibogaine, and norharman noradrenaline and adrenaline by cathinone, ephedrine, salsolinol GABA by arecaidine, and guvacine. Reserpine and deserpidine... 

Reserpine, Chlorpromazine and other Psycholeptic Drugs Reserpine depletes postganglionic sympathetic fibres of their noradrenaline and the peripheral sympathetic responses of animals which have been pretreated with reserpine are those which would be expected to follow loss of sympathetic transmitter . Thus, in adrenalectomized, reserpinized cats, stimulation of the splanchnic nerves does not produce the increase in blood pressure which is seen in non-reserpinized animals. Hexamethonium normally produces hypotension due to ganglionic blockade in the reserpinized animal it is without effect. Reserpine also causes a loss of adrenaline from the adrenal medulla. Since this adrenaline is liberated into the blood stream, it is not surprising that reserpine causes hyperglycaemia. 

S5mthesized via tyramine (Fig. 30-26), apparently functions in place of noradrenaline. Note fhe precursor-product relationship between dopamine, noradrenaline, and adrenaline. The synthetic pathways to these neurotransmitters involve decarboxylation and hydroxylahon, types of reacfion imporfanf in formation of other transmitters as well. The most important process for ferminafing fhe acfion of released catecholamine transmitters is reuptake by the neurons. High-affinity uptake systems transport the catecholamine molecules back into the neurons and then into the synaptic vesicles. The uptake is specifically blocked by the drug reserpine (Fig. 25-12).7 The dopamine transporter is a major binding site for cocaine (see Fig. 30-28).7 7-7Si Catecholamine trans-miffers are catabolized by two enzymes. One is the... 

The effects of adrenaline (epinephrine), noradrenaline (norepinephrine) and other directly-acting sympathomimetics are slightly increased in the presence of reserpine. 

Stimulant effect was reported [302]. In pharmacological tests, (119) potentiated many adrenaline like compounds and antagonized reserpine, tetrabenazine and phenothiazine. It has no anticholinergic, depressive, analgesic or local anaesthetic properties [303]. Notwithstanding structural analogy with harmaline (120), data on MAO inhibition were not presented. 

Carlsson, A., Rasmussen, E. B. and Kristiansen, P., The urinary excretion of adrenaline and noradrenaline by schizophrenic patients during reserpine treatment, J. Neurochem. 4, 318 (1959). 

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