Reserpine Epinephrine

Neuronal Norepinephrine Depleting Agents. Reserpine (Table 6) is the most active alkaloid derived from Rauwolfia serpentina. The principal antihypertensive mechanism of action primarily results from depletion of norepinephrine from peripheral sympathetic nerves and the brain adrenergic neurons. The result is a drastic decrease in the amount of norepinephrine released from these neurons, leading to decrease in vascular tone and lowering of blood pressure. Reserpine also depletes other transmitters including epinephrine, serotonin [50-67-9] dopamine [51-61-6] ... 

In the 1950s, the drug reserpine was studied because it lowered blood pressure by affecting catecholamines like norepinephrine, epinephrine, and dopamine. Researchers found that the early antidepressants reversed the effects of reserpine. They reasoned that antidepressants increased... 

A dose of 1 at 30 mg/kg increased the effects of intravenous doses of epinephrine at 5 g/kg and of dl-noreplnephrine at 10 ug/kg on both blood flow and blood pressure. Intravenous phenoxybenzamine at 15 mg/kg plus tolazollne at 2 mg/kg prevented almost completely the actions of I on blood pressure and blood flow Intravenous reserpine at 2 mg/kg increased markedly the effects of I at 30 mg/kg on blood pressure and peripheral resistance, but converted the usual immediate, small, temporary increase in blood flow into an immediate, small, temporary decrease. These various responses would be expected from either a mild sympathomimetic amine or an inhibitor of the breakdown of endogenous catecholamines Indeed, I at 10 M, was found to inhibit the monoamlneoxldase of the rat s liver. If the dose of I used in these experiments were distributed into the same fraction of the body water as that estimated for the human body,the concentration in the plasma would be about 9 times that stated above as the effective concentration for inhibiting the mono amine oxIdase. It is possible that inhibition of monoamlneoxldase by I plays a part in inducing the effects of the oxime on blood vessels and blood pressure. It is possible also that I interferes with reuptake of catecholamines by nerve endings this possibility seems not to have been explored. 

NE molecules are made inside into synaptic vesicles by the vesicular monoamine transporter (VMAT). This transport is an active, adenosine triphosphate (ATP)-requiring process. VMAT also transports DA, epinephrine and serotonin (5-HT). These hormones and transmitters are so-called monoamines (MO). Certain drugs, such as reserpine and tetrabenazine, inhibit the VMAT and suppress vesicular MO storage (Reinhard et al., 1988 Russo et al., 1994). 

Storage of norepinephrine in vesicles Dopamine is transported into synaptic vesicles by an amine transporter system that is also involved in the re-uptake of preformed norepinephrine. This carrier system is blocked by reserpine (see p. 78). Dopamine is hydroxylated to form norepinephrine by the enzyme, dopamine 3-hydroxylase. Synaptic vesicles contain dopamine or norepinephrine plus adenosine triphosphate and the 3-hydroxylase. Not all of the norepinephrine is packaged in vesicles some exists in a cytoplasmic pool that can be displaced. In the adrenal medulla, norepinephrine is methylated to yield epinephrine both are stored in chromaffin cells. On stimulation, the adrenal medulla releases about 85% epinephrine and 15% norepinephrine. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

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]. 

Acetylcholine Amphetamine Botulinum toxin Dopamine Epinephrine Metyrosine Norepinephrine Reserpine Tetrodotoxin Vesamicol... 

Reserpine is long-acting, and the postsynaptic neurons respond to the paucity of norepinephrine by "upregulating" (increasing) the number of receptors on the postsynaptic membrane. As a result, the postsynaptic terminal is supersensitive to direct sympathomi-metics. Consequently monoamine oxidase inhibitors (which prevent destruction of endogenous catecholamines such as norepinephrine and epinephrine) and direct sympathomimetics (Table 2.1 A) should be avoided in patients who have received reserpine. 

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

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