ALOPECIA AND CUTANEOUS ULCERATION IN RATS 331 occurred after a single subcutaneous injection of 0.5 mi. of the saline solution of the methoxamine hydrochloride. Therefore, a more conservative amount of 0.25 mi. was used for the highest doses administered. The sites of injections were on the middle of the head just back of the eyes or on the right or left flanks over the hip joints. In all of the 22 tests five rats of the same sex were used in each group. Comparison was made of actions following single or triple daily injections of aqueous solutions in the head or flank regions of male and female rats. The influence of the number of days of injections was also tabulated. In order to ascertain the effect of sex hormones on the action of methoxamine a second series deter- mined the derreal responses after the rats had also been treated with sex hormones. Male rats received 100 •,/kg. of estradiol and the females 1000 •,/kg. of methyl testosterone daily, both hormones given intra- peritoneally in aqueous suspensions for a week before and during the methoxamine injections. A third series incorporated a depot effect by injecting suspensions of the methoxamine hydrochloride in peanut oil. Daily observations and measurements were made of the injection sites for several weeks following the tests periods. Ages and weights of the animals were recorded during the tests. RESULTS Within twenty minutes after receiving the drug all of the rhts exhibited the usual intense pilomotor response of hair erection over the body. This effect lasted for some two to three hours or longer depending on the dosage. In the males, after three to four daily injections of 0.25 ml. in the head area, hair was lost about the sites of injections in irregular areas of 1-2 cm., across. Either one or three injections per day (Groups 1 and 2, Table 1) produced denuded areas in this region which persisted for several weeks after treatment had stopped. Saline controls produced no effect. When other male rats were injected in the flank region three times per day for a five-day period (Group 3), irregular areas 2-4 cm. across became devoid of hair by the end of the injection period. Only one male rat receiving a single injection per day (Group 4) in this flank area developed loss of hair although the other four showed some thinning of fur in the immediate area of the injection sites. However, if the injections were continued once a day for ten days in either the head or flank regions (Groups 5 and 6) all rats developed hairless areas. One animal receiving injections in the scalp also acquired a small necrotic area with scab formation. Younger males likewise developed hairless and some necrotic areas in either head or flank regions (Groups 7 and 8) when even 0.1 ml. of solution was ad- ministered once a day for ten days. Triple injections daily (Group 9) did not seem to increase this effect. Saline alone again had no visible action.

332 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Of the younger female rats, three months old, receiving 0.1 mi. daily in the head region (Group 10) only one showed any sign of hair loss. This one developed a small denuded area of less than 0.4 cm. across after five days of treatment. In the flank area, however, neither one nor three injections (Groups 11 and 12) per day caused any loss of hair. The older females over seven months of age did acquire furless areas fol- lowing ten days of injections either in the head area after single injections (Group 13) or in the flank after single or triple injections (Groups 14 and 15). Ulcerated areas with scab formation appeared on the flanks of two rats from each of the latter groups. TABLE 1.--INJECTIONS OF METHOXAMINE HYDROCHLORIDE IN SALINE SOLUTION Days Injec- of tions Age Wt., Dose, In)ec- per Results at Group Sex mos. gm. mi. Site t•on Day Injection Sites 1 M 52/4 350 0.25 2 M 51/4 350 0.25 3 M 5ø/4 350 0.25 4 M 53/4 350 0.25 5 M 61/4 350 0.25 6 M 61/4 350 7 M 31/4 350 8 M 31/4 350 9 M 41/s 350 10 F 3 2OO 11 F 3 200 12 F 3 200 13 F 71/4 230 14 F 73/4 230 0.25 01 01 01 01 0.1 0.1 0.1 0.1 15 F 7a/4 230 0.1 Hd 4 1 HA* 1-2 cm. across in 5 rats Hd 4 3 HA 1-2 cm. in 5 rats FI 5 3 HA 2-4 cm. in 5 rats FI 5 1 Ha 0.5 cm. in 1 rat Thin Ft in 4 rats Hd 10 1 HA 0.5-1 cm. in 5 rats Sc. $ on 1 rat F1 10 1 HA 2 cm. in 5 rats Hd 10 1 HA 0.5 cm. in 4 rats F1 10 1 HA 0.5-1 cm. in 2 rats Thin F 0,5-1 cm. in 3 rats FI 10 3 HA 1-1.5 cm. in 2 rats Thin F 0.5 cm. in 1 rat Sc. on 2 rats Hd 5 1 HA 0.5 cm. in 1 rat FI 5 1 No effects FI 5 3 No effects Hd ] 0 l HA 0.5-1 cm. in 5 rats F1 10 1 HA 1-3 cm. in 4 rats ThinF l X 2cm. in 1 rat Sc. on 2 rats F1 10 3 HA 1-2 cm. in 4 rats ThinF1 X lcm. inlrat Sc. on 2 rats * HA--Hairless areas, cm. across. t Thin F--Thinning fi•r, cm across. $ Sc.--Small scabs at sites of injections. Following the daily administration of estradiol (100 y/kg.) to the male rats and of methyl testosterone (1000 y/kg.) to the females for a week methoxamine hydrochloride was injected for a four-day period. Hairless areas appeared about injection sites in the males following single daily injections in the scalp (Group 16) and also in the flank following daily triple injections (Group 17) (see Table 2). Two animals in the former and one in the latter groups developed small scabs at the treatment sites. Some loss of hair appeared in the head region of three of the females