Pharmacology of Pempidine Tartrate

Pempidine tartrate (PMP) is a white powder and acts as a ganglion-blocking agent to treat severe hypertension [1]. Pempidine tartrate, like other highly active ganglion-blocking agents, was developed from tertiary alkylamines, itself weakly active, on the hypothesis that high activity was conferred by the presence in the molecule of a sterically hindered secondary or tertiary nitrogen atom.  The drug blocked sympathetic and parasympathetic ganglia; this action was slow in onset and protracted. It blocked neuromuscular transmission, but only about one hundredth as powerfully as ganglionic transmission. It caused a fall in amplitude and rate of the isolated heart and reduced coronary flow. All is well absorbed when administered orally [2].

Muggleton DF and Reading HW studied the absorption, metabolism and elimination of pempidine tartrate in the rat. When administered orally to rats pempidine tartrate was rapidly absorbed, the maximum concentration in plasma being attained after 30 min. The drug was preferentially taken up by erythrocytes and a red cell/plasma partition ratio of about 1.2 established with clinical doses. Pempidine tartrate was soon distributed throughout the body, including the cerebrospinal fluid, and the highest concentrations were found in kidney, spleen and liver. Pempidine tartrate also entered the foetus and passed thence into the amniotic fluid. Protein-binding of the drug occurred only to a very limited extent and there was little evidence that it was metabolized. Pempidine tartrate was excreted rapidly in urine during 24 hr. following oral administration [3].

Mechanism of Action

A wide variety of drugs, including pempidine tartrate, have been shown to inhibit the release of neurohypophysial hormones, and it is likely that there is more than one central nervous pathway for the release of neurohypophysial hormones. In 1968, Dyball studied the effect of drug on the release of vasopressin [4]. The results showed that all the acetylcholine antagonists had some effect on the release of vasopressin by calcium chloride, and pempidine tartrate inhibited the release only by the stimulus of calcium chloride injection.  Pempidine tartrate can be extracted from brain tissue after intraperitoneal injection in the rat, so it is also likely that the effects of calcium chloride and central vagal stimulation are exerted in the central nervous system so that inhibition of their effects. This implies that they too can cross the blood-brain barrier. Data also showed pempidine tartrate tended to inhibit the release of vasopressin in response to vagal stimulation and calcium chloride injection.  

References

[1] https://www.lexico.com/definition/pempidine

[2] A. SPINKS, E. H. P. YOUNG, J. A. FARRINGTON, AND D. DUNLOP, The Pharmacological Actions of Pempidine and its Ethyl homologue, Brit. J. Pharmacol. (1958), 13, 501-520.