Possible Rationale for Procaine (Gerovital H3) Therapy in Geriatrics: Inhibition of Monoamine Oxidase

Abstract

Gerovital H3, a specially formulated preparation of procaine hydrochloride, has been employed for several years in the treatment of various manifestations of aging. Heretofore, there has been no pharmacologic basis for its use in geriatric patients, although procaine hydrochloride and inhibitors of the enzyme, monoamine oxidase (MAO), are known to have many of the same pharmacologic actions. The relative effectiveness of Gerovital H3, commercial procaine hydrochloride (Novocain), and iproniazid as MAO inhibitors was studied by means of tests involving serotonin and kynuramine metabolism by rat-brain MAO. Gerovital H3 was a more effective MAO inhibitor than commercial procaine hydrochloride but was a less effective inhibitor than iproniazid. Moreover, Gerovital H3 seemed to have a selective affinity for certain of the multiple forms of MAO. These results, in view of the recent observations on MAO levels and aging, may offer a rationale for Gerovital H3 therapy in the elderly.

Procaine (Gerovital H3) Therapy: Mechanism of Inhibition of Monoamine Oxidase

“…The dilutional studies with pre‐incubated enzyme‐inhibitor complexes, as well as the other data, strongly indicate that GH3 is a reversible inhibitor of MAO, and that this inhibition is fully competitive as shown by the Lineweaver‐Burk and Dixon plots. These results, taken with the results of previous studies performed with GH3 (1, 2), show that GH3 is a weak (Ki 8.9 × 10 −5 ), reversible, fully competitive inhibitor of MAO. Robinson et al (16, 17) found an age‐dependent increase in MAO activity of human brain, plasma and platelets and a corresponding decrease in central monoamines.…”

“…The difference in the abilities of GH3 and iproniazid to inhibit M A 0 observed in previous studies (1) is of special interest since it may indicate that these two agents interact with the enzyme by different mechanisms. For example, iproniazid is an irreversible (6), mixed compet-…”

“…The difference in the abilities of GH3 and iproniazid to inhibit MAO observed in previous studies (1) is of special interest since it may indicate that these two agents interact with the enzyme by different mechanisms. For example, iproniazid is an irreversible (6), mixed competitive‐noncompetitive inhibitor of MAO (7, 8) that apparently produces the inhibition by combining with sulfhydryl groups at the active site on MAO (9).…”

“…Previous studies in this (1) and other laboratories (2) have dealt with the elucidation of a possible mechanism of action for the compound Gerovital H3 (GH3), a preparation of procaine hydrochloride used for the treatment of some of the manifestations of old age (3–5). The results of the preclinical studies (1, 2) demonstrated that GH3 produced a dose‐dependent inhibition of the enzyme, monoamine oxidase (MAO). Furthermore, it was observed that GH3 produced a greater inhibition of MAO than did plain procaine hydrochloride but a weaker inhibition than did iproniazid phosphate.…”

“…Furthermore, it was observed that GH3 produced a greater inhibition of MAO than did plain procaine hydrochloride but a weaker inhibition than did iproniazid phosphate. The GH3 used in the preclinical studies and for the treatment of geriatric patients was composed of a 2% solution of procaine hydrochloride, the formulation of which was modified during the manufacturing process by the addition of various substances 1 intended to increase the biologic half‐life of the active ingredient, procaine hydrochloride.…”