Previous studies on the filaricidal properties of various drugs in naturally acquired infections with Litomosoides carinii in cotton rats,1-5 Dirofilaria immitis in and Wuchereria bancrofti in human patients8? have been confined largely to organometallic compounds. With the exception of certain cyanine dyes: no chemical compound not containing antimony or arsenic has been shown to produce marked filaricidal activity in any of the above hosts. Moreover, the above classes of compounds produce their maximum effects when administered parenterally.During the course of a screening program for filaricides in these laboratories, using cotton rats naturally infected with Litornosoides carinii as test animals, marked activity was found with a number of piperazine compounds. The most active members of the series studied produce filaricidal effects in cotton rats quite different from any other known group of compounds, in that (1) an immediate reduction in microfilariae occurs following the first dose, (2) the adult worms are killed slowly, after prolonged treatment, and ( 3 ) oral administration is equally as effective as parenteral administration. Subsequent investigations showed that these effects could be carried over to Dirofilaria-infected dogs, and to human patients infected with Wuchereria bancrofti.The results obtained in cotton rats and dogs with various piperazines, and in particular with 1-diethylcarbamyl-4-methylpiperazine hydrochloride (Hetrazan), form the subject of this paper. The general procedures used for studying the action of chemical compounds in cotton rats and dogs have been discussed previously.1°The first piperazine compound found to produce a measurable effect against Litomosoides carinii was 1-carbethoxy-4-methylpiperazine hydrochloride. I n intraperitoneal doses ranging from 6.25 to 200 mg. per kg. twice daily, this compound produced marked reductions in circulating microfilariae (TABLE 1 ) . Oral doses within the same range were found to be equally effective against microfilariae. Reductions as high as 95 per cent occurred in some animals on the first day after treatment was initiated, and were sustained as long as treatment was continued. Very little effect with this compound could be demonstrated against adult worms, however, particularly in early stages of the investigation, and a number of related compounds were therefore prepared by our organic chemistry division in order to determine whether the activity could be enhanced.The piperazine nucleus itself showed no activity, nor did any of its components. A carbethoxy radical in position "l", with various substitu- Types of Piperazines Studied.(128)

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