lephetamine and Substance-Related-Disorders

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.

Topics: Anesthetics, Local; Antipsychotic Agents; Clonidine; Follow-Up Studies; Heroin Dependence; Humans; Methadone; Phenethylamines; Randomized Controlled Trials as Topic; Receptors, Opioid; Substance-Related Disorders

With the aim to split the pharmacological properties of lefetamine (CAS 14148-99-3), some structural modifications of this compound have been studied. The basic group of lefetamine has been shifted from the alkyl chain to the vicinal phenyl ring and the N-substitution has been changed. The dimethylaminomethyl derivatives and chiefly the o-morpholinometyhl exhibited a strong anti-visceral chemical antinociception activity stripped of thermal antinociception properties and physical dependence liability. Furthermore, through the introduction of a diethylaminomethyl group in the lefetamine structure some derivatives were selected exhibiting besided a significant increase in the anti-visceral chemical antinociception activity, remarkable local anesthetic properties.

Topics: Analgesics, Non-Narcotic; Anesthesia, Intravenous; Anesthetics, Local; Animals; Anura; Behavior, Animal; Female; Guinea Pigs; Lethal Dose 50; Male; Mice; Pain Measurement; Peripheral Nerves; Phenethylamines; Rabbits; Structure-Activity Relationship; Substance-Related Disorders

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.

Topics: Female; Male; Phenethylamines; Substance Withdrawal Syndrome; Substance-Related Disorders

A case of lefetamine abuse (0.9-1.8 g/day in 15-30 i.m. divided doses) is reported. In this patient, the administration of naloxone precipitated a mild opiate-like withdrawal syndrome, characterized by mydriasis, piloerection, yawning and a slight increase of blood pressure. The complete withdrawal of lefetamine, substituted by a placebo regimen, aggravated these symptoms. Furthermore, experimental results showed that lefetamine induced a naloxone-reversible inhibition of the guinea-pig ileum contractile response to electric field stimulation, and that naloxone pretreatment of mice prevented lefetamine antinociceptive activity in the hot-plate test. The clinical and experimental findings suggest that lefetamine has an opiate-like activity.

Topics: Animals; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Male; Mice; Middle Aged; Muscle Contraction; Muscle, Smooth; Naloxone; Nociceptors; Phenethylamines; Receptors, Opioid; Substance Withdrawal Syndrome; Substance-Related Disorders

The drug dependence potential of viloxazine was tested in 5 experiments on rhesus monkeys. In gross behavioral observation of normal monkeys the acute CNS effects of the drug were found to be very weak. Decrement of spontaneous motor activity and occasional eye-closing were observed with single doses higher than 16 mg/kg IV, IM and 128 mg/kg PO, while convulsions and death occured at 64 mg/kg IV and IM. Viloxazine did not suppress the morphine and barbital withdrawal signs in monkeys that had been made physically dependent on these drugs and withdrawal. In the test for physical dependence by repeated administration of the drug at 16 mg/kg IM twice daily for 31 days in normal monkeys, no observable withdrawal sign was developed in the naloxone precipitation and natural withdrawal tests. In intravenous self-administration experiments, a weak reinforcing effect was demonstrated in some monkeys, but the effect was extremely weak. Thus, viloxazine was found to be physical dependence-free and its overall dependence potential was regarded as very low.

Topics: Animals; Barbital; Behavior, Animal; Female; Haplorhini; Humans; Macaca mulatta; Male; Morphine Dependence; Morpholines; Phenethylamines; Substance Withdrawal Syndrome; Substance-Related Disorders; Viloxazine