Amphetamines

66 H. ISBELL & T. L. CHRU§CIEL AMPHETAMINES This subgroup includes 31 different compounds with variable abuse potential (Table XIII). Four of the drugs, amphetamine (S 167), dexamphetamine (S 171), methamphetamine (S 180) and phen- metrazine (S 186), have been extensively abused in various countries (for references see Table XIII), both orally and intravenously. The dependence potential of these four compounds has to be regarded as very high. The great degree of risk also has to be considered in relation to the limited proven therapeu- tic usefulness of these compounds. A small number of cases of abuse of amfepramone (S 166) has been reported in some countries,231e 232, 260, 261, 275 and compound S 193 (SPA) was misused fairly extensively in Japan as long as it was available without prescription. Thus both amfepramone and SPA must be assessed as having moderate depen- dence potential which, however, is less than the abuse liability of the four compounds described in the preceding paragraph. There is insufficient information concerning the dependence liability of some compounds sold as anorexiants: amfepentorex (S 165), amfecloral (S 164), benzphetamine (S 168), clobenzorex (S 170), chlorphentermine (S 169), fenfluramine (S 172), fludorex (S 173), furfenorex (S 174), mefenorex (S 177), mephentermine (S 178), metamfepramone (S 179), ortetamine (S 182), oxifentorex (S 183), pentorex (S 184), phendimetrazine (S 185), phen- termine (S 188) and 1-phenyl-2-nicotinylamino- propion (S 189). All of these anorexiant drugs must, by chemical and pharmacological analogy, be suspected of being potentially capable of causing dependence of the amphetamine type. Levamfetamine (S 176) is much less potent as a central stimulant than dexamphetamine but is as active as dexamphetamine as a peripheral sympatho- mimetic. No instance of abuse was found. The abuse potential of levamfetamine seems to be quite low. The remaining amphetamines (alfetamine, S 163; hydroxyamphetamine, S 175; methoxy- phenamine, S 181; phenpromethamine, S 187; phenylpropanolamine, S 190; prenylamine, S 191 and propylhexedrine, S 192) have only feeble central nervous system stimulant properties and are used primarily for peripheral sympathomimetic effect. They are judged to have quite low or no dependence potential. REFERENCES 227. Abdullah, A. H. (1968) Arch. int. Pharmacodyn., 176, 395-402 (Comparative study of anorectic activity of d-amphetamine, chlorphentermine and fenfluramine in autothioglucose obese and non- obese mice) 228. Bell, D. S. & Trethowan, W. H. (1961) J. nerv. ment. Dis., 133, 484-496 (Amphetamine addic- tion) 229. Bell, D. S. (1967) Med. J. Aust., 1, 41-45 (Addiction to stimulants) 230. Brit. med. J., 1962, 1, 670 (Purple Hearts) 231. Caplan, J. (1963) Canad. med. Ass. J., 88, 943-944 (Habituation to diethylpropion-Tenuate) 232. Clein, L. (1957) Brit. med. J., 1, 282 (Toxic psychoses caused by " Preludin") 233. Clein, L. S. & Benady, D. R. (1962) Brit. med. J., 2, 456 (Case of diethylpropion addiction) 234. Connell, P. H. (1958) Amphetamine psychosis, Chapman & Hall Ltd, London 235. Connell, P. H. (1966) J. Amer. med. Ass., 196, 718 (Clinical manifestations and treatment of amphe- tamine type dependence) 236. Connell, P. H. (1968) Proc. roy. Soc. Med., 61, 178-181 (Amphetamine dependence) 237. Connell, P. H. (1968) Practitioner, 200, 234-243 (The use and abuse of amphetamines) 238. Darling, H. F. (1961) Amer. J. Psychiat., 118, 558 (Addiction to phenmetrazine hydrochloride) 239. Durrant, B. W. (1965) Practitioner, 194, 649 (Amphetamine addiction) 240. Edison, C. R. (1968) J. Amer. med. 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E 10E c co U0 _Co E E mu 0 - 0 6 z co U- I Xs 0 Z 0 M0-0 \I/ 6 0 0 CL 0 E 0, I0 I z 1C4 I n I I 0-0 D E .la >1 c54) a D ._L 25 U) I I 'I ns C E la 0 C 0 0 E Cs a =010: I I z 0=0 , \ a - 73 Q. Z3 ci E- z I 0. z Cl)w 0. co z z w 0 co X3 m C 0 0 0 0 0 0 C 0 0D 0) It ei 0 0~~~~~~~~~~~~~~~~~~ CL ~~ ~0 0 00 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~co0-- C C 0O.co 30~ 0 0 0 'a0 C 0~~I 0~ 0~ .0 CCC s-0C"' 0). 0: 0o 0 C o 0 0 0 0) E0coE E2 E fl~ 0 0 0 0 E. .E zE zE :20 _ 0 0 00 "- 0 -. C 0 0 0 C 0 0 0 C L0 0 C" C C 0~~~~~~~~~~~~~~~~~~ o 0~~~~~ 0 0 0 0 0 U) C 0~~~~~~~ OC 0 C~~~~~~~~~~~~0 75 -u -c0E0 CC Z 0 0U . Z COC<0 2~ ~ ~~~~~~~~~~~~~ 00. C-i 0,-. ~ ~ . 0 U cco E Cc cC CO 0.0 CL0 0 z I U U-Z CL o a 0 I%0 C 0.aU) p I I x z ~~or~oU)I > q"~~ 2 wCL 022 .C 09 ~0 I U I 0) D z x c CIA U) 0) C E 0) C 0 0 z I ._ 2 2 -74 -2 b C) 0 CO) en > z 2 X m U) z -j U1) U) U) 0 z I- z U 0 CD 0 0 *0 C 0 0. I DEPENDENCE LIABILITY OF "NON-NARCOTIC " DRUGS 75 247. Hart, R. (1968) Brit. med. 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Psychiat., 112, 617-619 (Amphetamine intoxication and dependence in admissions to a psychiatric unit) 256. Kalant, 0. J. (1966) The amphetamines: toxicity and addiction (Brookside Monograph No. 5) University of Toronto Press, Toronto 257. Kiloh, L. G. & Brandon, S. (1962) Brit. med. J., 2, 40 (Habituation and addiction to amphetamines) 258. Knoll, J., Vizi, E. S. & Ecseri, Z. (1966) Arch. int. pharmacodyn., 159, 442-451 (Psychomimetic methylamphetamine derivatives) 259. Kramer, J. C., Fischman, V. & Littlefield, D. C. (1967) J. Amer. med. Ass., 201, 305-309 (Amphe- tamine abuse. Pattern and effects of high doses taken intravenously) 260. Kuenssberg, E. V. (1962) Brit. med. J., 2, 729-730 (Diethylpropion) 261. Kuenssberg, E. V. (1963) Brit. med. J., 2, 1406 (Diethylpropion and addiction) 262. Lachnit, V. (1965) Wien. Z. inn. Med., 46, 248-254 (On the use of so-called anorexigenic drugs) 263. Ladewig, D., Battegay, R. & Labhardt, F. (1969) Dtsch. med. 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(1968) Adolescent drug dependence, Pergamon Press, Oxford PIPERIDINE DERIVATIVES Methylphenidate (S 195; Table XIV) is marketed as an antidepressant drug. It has limited usefulness in the treatment of narcolepsy. For many years cases of abuse were rare but recently abuse of methylphenidate has occurred in the USA, 297-299 the United Kingdom and Sweden.244 When methylphenidate is taken intravenously in a high dose, it produces a clinical picture quite similar or identical to that caused by intravenous use of meth- amphetamine or phenmetrazine. Accordingly, it must be regarded as having high dependence liability coupled with limited proven therapeutic usefulness. A few cases ofabuse ofpipradrol (S 196) occurred 244 a number of years ago, but in recent years no new cases have been reported. Thus it is difficult to rate the dependence potential ofpipradrol but it must be judged, pending additional information, as being definite if somewhat less than that of methylpheni- date. 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