Reserpine

July 2, 2020 Rima Pharmacology, Pharmacology of anti-hypertensive agents 0

  • Reserpine is a Rauwolfia alkaloid obtained from root of the plant Rauwolfia serpentina or Sarpagandha. Reserpine was used in India from ancient times for conditions like snakebite, fever and insanity. Its molecular structure was elucidated in 1953 and first total synthesis was accomplished in 1958.
  • It was first approved by FDA in 1955 for use in hypertension.

Mechanism of Action of reserpine

  • Reserpine causes depletion of catecholamines- adrenaline, nor-adrenaline (NA), dopamine and serotonin from various storage sites in the body.
  • It binds tightly to adrenergic storage vesicle in central and peripheral adrenergic neurons and inhibit vesicular monoamine transporter (VMAT-2) which facilitate NA uptake and storage. This causes loss of storage capacity in nerve terminal resulting in leakage of catecholamines in cytoplasm where they are metabolized. The overall result is depletion of catecholamines.
  • Similar is the case with storage sites of serotonin.
  • Depletion results in a lack of active transmitter discharge from nerve endings upon nerve depolarization, and consequently leads to a decreased heart rate and decreased arterial blood pressure as well as sedative effects.

Pharmacological Effects of reserpine

Cardiovascular System

  • When administered through IV route, hypotensive effect appears after 30 minutes. Maximum effect develops after 2-4 weeks of repeated oral medication.
  • Hypotension is usually accompanied by bradycardia. Hypotensive effect remains even after missing a daily dose.
  •  When used with other anti-hypertensive agents specially diuretics, it shows synergistic effect.

CNS (Central Nervous System)

  • It causes depletion of serotonin and dopamine from CNS and shows sedative and anti-psychotic actions.

GIT (Gastrointestinal Tract)

  • It increases gastric acid secretion and augment peristaltic movement. Hence, it is used to induce peptic ulcer in experimental animals.

Pharmacokinetics of reserpine

  • It is administered through oral and parenteral route. It is lipid soluble, can penetrate blood brain barrier (BBB). and  is distributed in various parts of CNS.
  • When administered through oral route, its central and peripheral effects are developed slowly and maintained for long period of time even after complete elimination of the drug.
  • It is entirely metabolized and only about 1% is excreted unchanged. However, its metabolic pathway is not known.

Therapeutic Uses

  • To treat high blood pressure. However, its use as anti-hypertensive is declined due to CNS related side effects.
  • To treat schizophrenia. Used as adjunctive treatment in combination with other anti-psychotics.

Adverse Effects

  • Most adverse effects occur due to its action on CNS. The most common adverse effects are sedation, inability to concentrate and perform complex task.
  • Mental depression is most serious, dose-related adverse effect which is very uncommon. Reserpine must be discontinued at the first sign of depression.
  • Large dose of reserpine can cause parkinsonism due to dopamine depletion. Large doses can also cause endocrine disturbance like gynecomastia and impotence in male and reduction of fertility in female.
  • Some other side effects are weight gain, orthostatic hypotension, allergic manifestation, nasal congestion and increased gastric acid secretion.

Drug Interaction

  • Concurrent administration with direct or indirect sympathomimetic agents should be monitored. It can prolong action of direct acting amines like epinephrine, phenylephrine and inhibit activity of indirect acting amines like ephedrine and tyramine.
  • When used together with MAO inhibitor, it can produce rise in BP (reserpine reversal effect). So, MAO inhibitors should be avoided or used with caution.
  • It should be used cautiously with digitalis and quinidine.

Contraindication

  • It should be contraindicated in patients with known hypersensitivity.
  • Should be avoided in patients with mental depression or history of depression, active peptic ulcer, ulcerative colitis and patients receiving electroconvulsive therapy.
  • It should be avoided in breastfeeding if possible.

Reference

  1. https://pubchem.ncbi.nlm.nih.gov/compound/reserpine
  2. https://www.cochrane.org/CD007655/HTN_reserpine-lowering-blood-pressure
  3. https://www.drugs.com/pro/reserpine.html
  4. Khan ZA, Shahzad SA, Anjum A, Bale AT, Naqvi SAR. Synthetic approaches toward the reserpine. Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry. 2018; 48(10): 1128-1147.
  5. Fischer E, Heller B. Pharmacology of the Mechanism of Certain Effects of Reserpine in the Rat. Nature. 1967; 216: 1221–1222.
  6. Pharmacology and pharmacotherapeutics. 24th edition.
  7. Goodman and Gillman Manual of Pharmacology and Therapeutics.