PHARMACOLOGY OF N-(2-FURFURYL)-N-(2-PYRIDYL)-N',N'-DIMETHYLETHYLENEDIAMINE FUMARATE (METHAFURYLENE FUMARATE). I. ANTIHISTAMINIC PROPERTIES OF THIS COMPOUND AND ITS 5-CHLORO AND 5-BROMO DERIVATIVES

¹ Division of Pharmacology, Eaton Laboratories, Inc., Norwich, New York

Methafurylene fumarate (F-151) and its 5-chloro (F-176) and 5-bromo (F-180) derivatives are potent antihistaminic agents as determined by their antagonistic effects toward histamine on the isolated ileal strip and tracheal chain of the guinea pig and on the cat's blood pressure. The methyl analog (F-172) is only about one-fiftieth as potent.

These compounds are specific antagonists for histamine in that, although they also relax spasms of smooth muscle induced by acetylcholine, barium chloride, and epinephrine, the doses required for these antispasmodic effects are generally in the neighborhood of ten thousand times the antihistaminic dose.

Assays indicate that F-151 and F-176 are essentially of the same potency as U-95 when compared on the basis of molecular equivalents of the bases. The available data indicate that F-180 may be twice as potent.

Intraperitoneal administration of F-151 or U-95, in doses of 1 or 2 mgm./kgm., afforded significant protection of guinea pigs from histamine aerosol. Duration of protection in some animals was as long as seven hours.

Large doses of these compounds produce some histamine-like effects.

The LD₅₀'s for F-151, F-176, and F-18O, orally in CF # 1 male mice, were signlficantly higher than for U-95, suggesting better therapeutic ratios.