Two behavioural indices for psychotomimetic activity have been used to elucidate the probable role of methoxy group configuration in the mescaline molecule. The first method using a shuttle box CAR has been reported previously in this series. The second is based on the Sidman Avoidance schedule and utilizes the Bovet-Gatti profiles. Our results indicate that only two analogues of mescaline are active-the 2,3,4,5 and 2,3,4,5,6 compounds. This indicates that the 3,4,5 configuration is necessary and that adding extra methoxy groups increases activity. The great activity of the penta methoxy compound may be due to the fact that this compound substituted in the 2 and 6 positions cannot be metabolized by mescaline oxidase. The significance of these results is discussed.
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Appel, J. B., and D. X. Freedman: The relative potencies of psychotomimetic drugs. Life Sci. 4, 2181–2186 (1966).
Benington, F., R. D. Morin, and L. C. Clark jr.: Mescaline Analogs. J. Org. Chem. I, 19, 11–16 (1954–1958).; II, 20, 102–108; III, 20, 1292–1296; IV, 20, 1454 to 1457; V, 21, 1470–1472; VI, 21, 1545–1546; VII, 22, 332–333; VIII, 23, 19–23; IX, 23, 2034–2036 (1954–1958).
Bovet, D., and G. L. Gatti: Pharmacology of instrumental avoidance conditioning. Proc. II Int. Pharm. Meeting, Prague, 1963, pp. 75–89.
Clark, L. C., jr., F. Benington, and R. D. Morin: The effects of ring-methoxyl groups on biological deamination of phenethylamines. J. med. Chem. 8, 353–355 (1965).
Ernst, H. M.: Phenomena of the hypokinetic rigid types caused by O-methylation of dopamine in the para-position. Nature (Lond.) 193, 178–179 (1962).
—: Relation between the structure of certain methoxy phenyl ethylamine derivatives and the occurrence of a hypokinetic rigid syndrome. Psychopharmacologia (Berl.) 7, 383–390 (1965).
Hollister, L. E., and A. J. Friedhoff: Effects of 3,4-dimethoxyphenylethylamine in man. Nature (Lond.) 210, 1377–1378 (1966).
Jong, H. de: Experimental Catatonia. Baltimore: Williams & Wilkins 1945.
Noteboom, L.: Experimental catatonia by means of derivatives of mescaline and adrenaline. Proc. roy. Acad. Sci. 37, 562–572 (1934).
Pollin, W., P. V. Cardon, and S. S. Kety: Effects of amino acid feedings in schizophrenic patients treated with iproniazid. Science 133, 104 (1961).
Schopp, R. T., W. F. Kreutter, and S. V. Guzak: Neuromyal blocking action of mescaline. Amer. J. Physiol. 200, 1226–1228 (1961).
Shulgin, A. T.: Psychotomimetic amphetamines. Methoxy 3,4-dialkoxyamphetamines. Experientia (Basel) 20, 1–4 (1964).
- Personal communication (1966).
Slotta, K., u. T. Müller: Über den Abbau des Mescalins und mescalinähnlicher Stoffe im Organismus. Z. physiol. Chem. 238, 14–22 (1936).
Smythies, J. R., and E. A. Sykes: The effect of mescaline upon the conditioned avoidance response in the rat. Psychopharmacologia (Berl.) 6, 163–172 (1964).
— —: Structure-activity relationship studies on mescaline: The effect of dimethoxyphenylethylamine and N.N-dimethyl mescaline on the conditioned avoidance responses in the rat. Psychopharmacologia (Berl.) 8, 324–330 (1966).
— —, and C. P. Lord: Structure-activity relationship studies on mescaline. II. Tolerance and non-tolerance between mescaline and its analogues in rat. Psychopharmacologia (Berl.) 9, 434–446 (1966).
Vojtechovsky, M.: Personal communication (1966).
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Smythies, J.R., Bradley, R.J., Johnston, V.S. et al. Structure-activity relationship studies on mescaline. Psychopharmacologia 10, 379–387 (1967). https://doi.org/10.1007/BF00403978
- Methoxy Group
- Great Activity
- Relationship Study