Drug Alcohol Depend. 1989 Oct;24(2):95-101.
Lefetamine: new abuse of an old drug--clinical evaluation of opioid activity.
Mannelli P, Janiri L, De Marinis M, Tempesta E
Dept. of Psychiatry, Faculty of Medicine, Catholic University of The Sacred Heart, Rome, Italy.
Lefetamine (SPA) combining amphetamine with opioid-like effects, a drug of wide abuse in Japan in the fifties, has now been introduced as such in Italy. In this study the drug was tested to verify its resemblance to opiates. Ten lefetamine abusers were hospitalized and then subjected to naloxone- and pentazocine-tests and detoxified. Moreover, lefetamine was administered to ten opiate addicts with an acute withdrawal syndrome and to ten methadone-treated addicts. The naloxone-test was positive and pentazocine could be substituted for lefetamine. Lefetamine was able to relieve opiate withdrawal and did not precipitate withdrawal symptoms in stabilized opiate addicts. It is concluded that lefetamine may act as an opioid partial agonist.
Farmaco. 1989 Sep;44(9):763-77.
Synthesis, neuropsychopharmacological effects and analgesic-antiinflammatory activities of pyrrole analogues of lefetamine.
Massa S, Stefancich G, Artico M, Corelli F, Silvestri R, Pantaleoni GC, Fanini D, Palumbo G, Giorgi R
Dipartimento di Studi Farmaceutici, Facolta di Farmacia, Universita degli Studi di Roma La Sapienza, Italy.
The synthesis of pyrrole analogues of the analgesic drug lefetamine is reported. These derivatives bear the 1-phenyl-2-(1H-pyrrol-1-yl)ethylamino moiety. Compounds were evaluated for analgesic activities in mice by the hot plate and Randall-Selitto tests. Antiinflammatory activity was tested by the carrageenan-induced rat paw edema method. General neuropsychopharmacological effects were also screened. The most interesting compound, N,N-dimethyl-1-phenyl-2-(1H-pyrrol-1-yl)ethylamine, showed an analgesic effect comparable to that of lefetamine, but devoid of the neurotoxicity of this drug.
Br J Addict. 1989 Jan;84(1):89-95.
Lephetamine abuse and dependence: clinical effects and withdrawal syndrome.
Janiri L, Mannelli P, Pirrongelli C, Lo Monaco M, Tempesta E
Lephetamine (L-SPA) is a compound with central analgesic and anti-inflammatory action, recently reported to be abused in Italy. In this study, cases of L-SPA abuse were recorded. The survey included 15 patients who were assessed for effects caused by using L-SPA and induced by withdrawal. Moreover L-SPA was administered to 15 volunteers. L-SPA displayed effects partly similar to opiates and its withdrawal caused both subjective and objective symptoms. It is concluded that L-SPA exhibits abuse liability and dependence potential of a certain degree.
Pharmacol Res Commun 1985 May;17(5):471-8
Opioid activity of lefetamine.
De Montis MG, Devoto P, Bucarelli A, Tagliamonte A
In mice lefetamine, at the dose of 50 mg/kg produces motor hyperactivity and at the dose of 60 mg/kg produces analgesia. Both effects are abolished by naloxone. Displacement studies by using [3H]-Naloxone (Nx), [3H]-D-Ala-Met-Enkephalinamide (DAMA) and [3H]-Ethylketocyclazocine (EKC) showed that lefetamine competes with all these opiates with an affinity 50 times lower than that of morphine. The displacing capacity of lefetamine is decreased in the presence of 50 mM Na+. It is concluded that lefetamine is an opioid agonist.
Neuropharmacology 1989 Dec;28(12):1405-10
Dual effects of lephetamine on spontaneous and evoked neuronal firing in the somatosensory cortex of the rat.
Janiri L, Persico AM, Tempesta E
Department of Psychiatry and Psychology, Catholic University of the Sacred Heart, Rome, Italy.
Lephetamine is a central analgesic, recently shown to be abused by drug addicts and to induce dependence in humans. The drug was applied microiontophoretically on single neurones of the somatosensory cortex of the rat in vivo. Its activity on the spontaneous and evoked firing rate was recorded. Morphine and naloxone were employed to verify the hypothesis that a mu-opiate mechanism of action could be involved. The most frequent response evoked by lephetamine was a dose-dependent excitation non-reversible by naloxone. On the other hand, units inhibited or apparently unaffected by the drug, showed a selective anti-glutamate (and partly anti-acetylcholine) effect, which was reversed by either systemically- or iontophoretically-administered naloxone. Long-lasting (8-12 min) applications of lephetamine caused a progressive desensitization of cortical neurones to the inhibitory and anti-glutamate effect. The inhibitory activity of lephetamine and morphine was additive and an increased neuronal excitability was shown by a post-inhibitory rebound of glutamate-induced neuronal activity. The action exerted by lephetamine on glutamate-induced excitations and on postsynaptic excitability, its reversibility by naloxone and the occurrence of acute tolerance allow the conclusion that only the inhibitory effect of lephetamine is mediated by an opioid mechanism. The lephetamine-induced excitations, not reversed by naloxone, are difficult to interpret as opioid-mediated.
Apparently this drug is quite old and has been abused in Japan and Italy. Learn something new every day. I believe synthesis would be quite easy with the corresponding ketone and amine. That would give a mixture of d,l-lefetamine which could possibly have the effects of the analgesic for the l and the dopamine release by the d.
