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It is an alkaloid extracted from the roots of a plant, Rauwolfia serpentine, a climbing shrub native to India, a genus of plants in the Apocynaceae family.
The flowers are small and generally white or greenish-white in color. Its function is as an antihypertensive and antipsychotic for oral administration.
This drug has been used in the past, now it has fewer dangerous side effects (it can even lead to suicide).
Applications
Reserpine was isolated in 1952. Reading Indian biomedical literature indicates that it was used for the treatment of mental disorders, fever, snakebites and by Mahatma Gandhi as a tranquilizer .
The first synthesis of the drug took place in 1958. Reserpine was the first drug found to interfere with the autonomic nervous system (ANS).
The molecule
Its chemical name is methyl 18β-hydroxy-11,17α-dimethoxy-3β, 20α-yohimban-16β-carboxylate 3,4,5-trimethoxybenzoate (ester).
Reserpine is derived from tryptophan and is converted by the enzyme tryptophan decarboxylase to tryptamine. Tryptamine combines with secologanin by the enzyme strictosidin synthetase.
Reserpine is made up of strictosidin with several enzymatic steps.
Pharmacokinetics
Reserpine is characterized by a slow onset of action and sustained effects. Reserpine is extensively bound (95%) to plasma proteins.
Reserpine is almost completely metabolized in the body, with only about 1% excreted as unchanged drug in the urine.
Mecanismo molecular
Reserpine blocks the vesicular catecholamine transporter and this interference causes the loss of the role of vesicles in the capture and storage of biogenic amines.
This happens throughout the body, but the important effects are on the nervous system.
Reserpine remains bound for long periods of time. The adrenal gland is less depleted. Reserpine is irreversibly bound to the gallbladder membrane.
Nerve endings lose their ability to concentrate and store norepinephrine and dopamine.
Catecholamines leak into the cytoplasm, where they are metabolized by intraneuronal monoamine oxidase and little or no active transmitter is discharged from nerve endings when depolarized.
The overall result is a pharmacologic sympathectomy.
Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles
The loss of catecholamines is important for the antihypertensive role of the drug.
Low-dose reserpine can be used for the treatment of hypertension because it blocks various sympathetic actions (peripheral vascular resistance, blood pressure, heart, renin-angiotensin system).
Reserpine and hypertension
It should be noted that reserpine enters the brain and depletion of brain amine stores causes sedation, mental depression , and symptoms of parkinsonism.
In fact, Mahatma Gandhi used reserpine as a tranquilizer and a sedative substance. These are the most important side effects for which they advise not to use reserpine for the treatment of antihypertension.
Antihypertensive treatment should not be standard for all patients, but you can use many different medications thanks to the history and genome of the patient.
The world is full of antihypertensive drugs, now the doctor can choose the most important ones.
Reserpine is also useful for the treatment of agitated psychotic states (eg, schizophrenia, Huntington’s chorea, and hyperkinetic diseases).
Reserpine helps decrease renal and endocrine hypertension.
Contraindications, adverse reactions and interactions
The strong inhibition of reserpine activity allows for increased parasympathetic activity. The effects of reserpine overdose should be treated symptomatically.
High dose:
- Hypersensitivity (purpura and rash).
- Mental depression (suicidal tendencies).
- Active peptic ulcer and ulcerative colitis .
Adverse reactions:
- Vomiting
- Diarrhea.
- Arrhythmias
- Syncope.
- Bradicardia.
- Breathlessness .
- Epistaxis.
- Rare parkinsonian syndrome and other symptoms of the extrapyramidal tract.
- Dizziness
- Headache.
- Paradoxical anxiety.
- Depression.
- Nervousness.
- Nightmares.
- Drowsiness.
- Muscle pains.
- Deafness.
- Optic atrophy.
- Hypersensitivity reactions (pruritus).
Reserpine increases gastrointestinal motility, so the doctor should know the patient’s history (do not take reserpine if you had a peptic ulcer).
Administration of reserpine during pregnancy has been shown to be teratogenic.
Reserpine crosses the placental barrier and increases respiratory tract secretions, nasal congestion, cyanosis, and anorexia in newborns of reserpine-treated mothers.
MAO inhibitors should be avoided or used with extreme caution. Concomitant use of tricyclic antidepressants may decrease the antihypertensive effect of reserpine.
The action of indirect-acting amines (ephedrine, tyramine, amphetamines) was inhibited when reserpine was administered.
Reserpine should be used with caution with digitalis and quinidine.
The modern use of reserpine
The use of reserpine has been discontinued in the UK for a few years due to its numerous interactions and side effects.
With the availability of newer drugs that are effective and well tolerated, the use of reserpine has decreased due to its side effects.
But there are now many studies in which reserpine and diuretics are given to treat hypertension (reserpine can cause significant sodium and fluid retention, and must be given with a diuretic).
Reserpine is one of the few antihypertensive drugs that has been shown in randomized controlled trials to reduce mortality.
