43-Y l-,'.Iethyl-d-lysergic acid butanolamide tartrate (Ui'@,iL-491, V-A-23). Investigation of the psychotorpimetic potency of,this compound (rrethyl methergine-) was undertaken because It is approximately 2.5 time's as po'tent as LSD in blocking serotoni-n- Induced contractions in the isola2ted rat's uterus and is 4--@;. times as potent as ,LSD in blocking the serotoniri-ir-duced edema in the rat.te paw (1).. It was, therefore, of interest because of the hypotheses relating the LSD,psychosis to serotcnin blockade in the central nervous system. METFODS Sub,lects. Thirteen adult, negro male former morphine addic4ts wi'thout signiflcant physical or mental disease volunteered for the experiments. All had experienced the effects of LSD in previous experiments. Pac?e 2 Drizas. Were given In solution at 8 a.in. with the patients fasting. In preliminary experiments the dose'of V-A-23 was elevated cautiously from 0.5 mg/70 kg to 5.0 mg/70 kg. In the final experiment all 13 subjects recei'ved 5.0 mg/7(@ kg of V-A-23. 2 Observations. The following observations were made at hourly intervals twice before;,-and eight times after the drug* pupillary diameter, s@stolic blood pressure, threshold for the y kneejerk, the LSD-q@iestionnaire,, and A short mental status examination. Methods followed were those described by Isbell et al (2), as,were the methods2 of analyzing tlie data (3). RESULTS In the preliminary experiments no psychosomimetic effects were.reported or observed with doses of 0.5 to 5.0 mg/70 kg of V-@.A.-@3 (8 subjects). In the final 'experi'ments, 2 of the 13 subjects reported psychotomimetic effects similar to those of LSD. Their symptoms included visual perceptual distortion, depersonalization, and optical hallucinations. Both were, however, very sensitive to LSD and both were regarded as being suggestible. One was a consistent placebo reactor. Significant pupillary dilatation did not occur'in either Instance. Symptoms in the remaining patients were not LSD-like and included sleepi- ness (6 of 13), nausea (4 of 13),4-and headache (I of 13). PaGe -The obs&rvations are summarized in Table I and are comp red a with data obtained on 9 subjects in another experiment after placebo and 1.0 and.1.5 mcg/kg of LSD. Significant elevations in blood pressure and pupillary diamettr were observed, but the 2 change in the pupils was small, even though significant. A sionificant decrease in-the threshold for the kneejerk also occurred. DISCUSSION The results are somewhat puzzling in.that the pattern of change in the objective measurements was LSD-like, but was, @with the exception of the 2 patients mentioned above, not correlated with mental charges of tl2,,e LSD-type. It seems safe to state that if V-A-23 is a psychotomirretic, it is far less potent than LSD. Thus another example is added to the list of compounds that are potent inhibitors of peripheral actions of serotonin, but are not potent psychotomimetics. SU,%I%@P.RY 1. In doses of 71 mcg/kg (5-0 mg/70 k8g), 1-Methyl-d.' lysergic acid butanolamide tartrate did not consistently cause psychotomir,.etic effects, although significant elevations of blood pres sure, decrease in the threshold for the kneejerk and dilatation of the puoils did occur. Pa-ge REFERENCES 1. DOEPFNAR, 19. and CF-RLETTI, A.: Com;arison of lysergic acid derivatives and antihistamir-es as inhibitors of the ede.,ra provoked in the ratls paw by serotonin. Internat. Arch. Allerg. and Appl. Immunol., 122: 82-91' 1958. 2. ISBELL, H., BELLEVILLE..,R. E.3 FRASEPL H. F., @VIKLE--4, A., and LOC-AN C. R.: Studies on lyser@rc acid diethylai-aide: 1. Effects in former morphine addicts and developr,,ent of t4.olerance during chronic intoxication. A.,@.I.A. Arch. Neurol. & Psychiat.,, 76: 468-478 (Nov.) 1956. 3. ISBELL, H. -and LOriAiN, C. R.: Studies on lysergic acid diethylamide (LSD-25). Ill. Attempts to attenuate the LSD- reaction in man by pretreatment with neurohumoral blocking agents. A.M.A. Arch. Neurol. & Psychiat., §1: 20-27, 1959. Table 1. Comparison of the Effects of 1-Methyl-d-lysergic acid butanolamide (UML-491, V-A-23) with Thos'e of LSD-25. .DRUG AND DOSE (mcgZkgl_' 2 Placebot LSDI LSDI V-A-232 tll:'ASURE 1.0 1.5 71.5 (5-0 mg/70 lg) 14@ti)lllary Size 0.2 I.I@ 10.2 t 1.18 15.0 i 2.1 i.i Blood Pressure +i .6 13.5 64.8 10.9 81.cf io.1 5 +94.6 17.5 Patellar Reflex +20.7 11.1 -50-9 ± 31 -7@.9 ± 221.7 55.8 i,.ii.iiiiber of Positive Responses .0.1 0.3 57 ± 23.2 98 ± 26.6 16.3 7.6 oii Questionnaire (71iiiical Grade 0'± 0 22 9 0.38 2.8 0.17 0.46± 0.33 1. Means standard errors of observations on 9 subjects. 2. Means standard errors of observations on 13 subjects.