Pharmacokinetics and central nervous system toxicity of declopramide (3-chloroprocainamide) in rats and mice

Anticancer Drugs. 1999 Jan;10(1):79-88. doi: 10.1097/00001813-199901000-00010.


Declopramide (3-chloroprocainamide) has been identified in previous studies as a representative of a new class of chemosensitizers. In this study, the toxicity and pharmacokinetics of declopramide have been investigated and compared with a structural analog, metoclopramide (MCA). Declopramide has not induced central nervous system (CNS)-related side effects in rats at doses up to 200 mg/kg, whereas MCA does at 12.5 mg/kg. In addition, declopramide did not bind to dopamine D2 receptors in subcellular preparations at doses up to 100 microM, whereas MCA showed affinity at 1 microM. Declopramide bound with affinity to 5-hydroxytryptamine3 receptors which are important in controlling vomiting. In contrast to MCA, declopramide has a rapid clearance from serum, a lower tissue concentration (about 15-fold lower than MCA) and a lower oral bioavailability (about 6-fold lower than MCA). However, declopramide was shown in vitro to possess a higher tumor cell absorption rate. One of the main metabolites of declopramide was identified as N-acetyl declopramide. Taken together, these data suggest that the clinical development of declopramide as a sensitizer of radio- and chemotherapies is an improvement over MCA, because it can be administered in a high dose and is devoid of CNS side effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antiemetics / pharmacokinetics
  • Antiemetics / toxicity
  • Biological Availability
  • Central Nervous System / drug effects*
  • Dopamine Antagonists / pharmacokinetics
  • Dopamine Antagonists / toxicity
  • Dose-Response Relationship, Drug
  • Female
  • Metoclopramide / pharmacokinetics
  • Metoclopramide / toxicity
  • Mice
  • Mice, SCID
  • Procainamide / analogs & derivatives*
  • Procainamide / metabolism
  • Procainamide / pharmacokinetics
  • Procainamide / toxicity
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT3
  • Sleep Stages / drug effects
  • Tissue Distribution


  • Antiemetics
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • declopramide
  • Procainamide
  • Metoclopramide