THE ANTIFILARIAL ACTION OF CYANINE DYES

II. Selection of 1'-ethyl-3, 6-dimethyl-2-phenyl-4-pyrimido-2'-cyanine Chloride (# 863) for Further Study as a Potential Antifilarial Agent

¹ Department of Pharmacology, School of Medicine, Western Reserve University, Cleveland, Ohio

(1) Twelve cyanine dyes, reported in a previous paper (1) to be the most active of a larger series against the filarial parasite, L. carinii, of the cotton rat, were studied further with regard to their efficacy by various routes of administration and to their relative suitability for clinical trial in human filariases.

(2) In contrast to the marked chemotherapeutic activity exerted by these compounds following intraperitoneal administration to infested cotton rats, oral administration even of massive doses resulted in only occasional cures.

(3) Cures were produced following subcutaneous administration, but the therapeutic indices were less favorable than those obtained when the intraperitoneal route was used. Furthermore, the compounds produced, at the sites of injection, local tissue injury of a sufficient degree to preclude their administration by this route to human patients.

(4) One of the intrinsically most active compounds, 1'-ethyl-3,6-dimethyl-2- phenyl-4-pyrimido-2'-cyanine chloride, was selected for further study using the intravenous route of administration, since it produced less circulatory depression and less local tissue injury than any of the other compounds studied.

(5) This compound was found capable of producing cures in infested cotton rats when six doses each of 1.0 mgm. per kgm. were administered intravenously at either 24-hour, 72-hour, or weekly intervals. Lethal results followed the intravenous administration of single doses of 15 mgm. per kgm., and some animals were killed by the repeated injection of 10 mgm. per kgm., at intervals of one day. The wide range of dosage intervals over which the therapy was successful is discussed and the conclusion is drawn that the chemotherapeutic effect of the drug is related more directly, within limits, to the total amount of drug administered than it is to the frequency of administration.

(6) The course of the microfilaremia following administration of cyanines to cotton rats infested with L. carinii, and to dogs infested with D. immitis is described, as is the failure of these dyes to kill adult worms in the latter case. The implications for the clinical trial of # 863 in patients harboring W. bancrofti are discussed.