HYDROXYPROPYL THEOPHYLLINE: A PHARMACOLOGICAL COMPARISON WITH OTHER THEOPHYLLINE PREPARATIONS

¹ Department of Pharmacology, Research Division, Schering Corporation, Bloomfield, New Jersey

Hydroxypropyl theophylline (HPT) and choline theophyllinate (CHT) were approximately one-half as potent as theophylline ethylenediamine (AM) in relaxing the unstimulated guinea pig tracheal chain. AM also was demonstrably more potent than HPT and CHT in antagonizing tracheal muscle contractions induced with histamine or acetylcholine.

In the perfused guinea pig lung AM was demonstrably more effective than HPT and approximately two times as effective as CHT in blocking bronchospasm induced with histamine or methacholine.

Oral pretreatment with HPT or AM protected guinea pigs against lethal asphyxial collapse following exposure to aerosolized histamine. The potency of HPT in this regard was greater than that of CHT but less than that of AM. Hyperactivity and convulsive side effects were observed after higher doses of AM or CHT but did not occur after HPT.

The oral emetic dose of HPT in dogs was greater than two and one-half times that of AM or CHT.

The cardiovascular activity of HPT and AM was characterized by hypotension, cardiac stimulation, tachycardia and femoral and coronary vasodilatation. AM had approximately twice the effect of HPT on the heart rate, cardiac contraction strength and blood pressure. Both compounds were of approximately equal activity in increasing coronary blood flow, whereas AM produced a demonstrably greater effect than HPT on peripheral flow.

The toxicity of HPT by various routes of administration in mice and rats was at least one-half that found for AM or CHT. HPT also exhibited much less central nervous stimulating activity than AM in these species.

Six-month chronic toxicity studies in rats and dogs revealed no gross or microscopic abnormalities of blood or organ samples which could be attributed to the administration of HPT or AM.