THE PHARMACOLOGY OF 5-(3-PYRIDYL) TETRAZOLE, A HYPOCHOLESTEREMIC LIPOLYSIS INHIBITOR

¹ Medical Research Laboratories, Chas. Pfizer & Co., Inc., Groton, Connecticut

5-(3-Pyridyl) tetrazole (P-3-T) inhibited the norepinephrine-induced lipolysis in vitro and reduced fasting plasma free fatty acid (FFA) values in rats. The P-3-T-induced reduction in plasma FFA values persisted longer than that induced by nicotinic acid and is not associated with a rebound of FFA to supernormal levels. Like nicotinic acid, P-3-T retained the ability to depress FFA levels with repeated administration. An infusion of P-3-T into fasted, anesthetized dogs caused a fall in plasma FFA levels and a concomitant decrease in plasma triglycerides. In humans, P-3-T caused a decrease in plasma FFA values with no indication of FFA rebound. Upon repeated p.o. administration to humans, P-3-T decreased plasma cholesterol levels within 7 to 10 days of treatment. A mechanism for the hypocholesteremic action of P-3-T based on its antilipolytic effects is proposed. The effects of a variety of agents on hepatic lipoprotein synthesis are discussed in relation to the hypocholesteremic effects of P-3-T.