Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake and release in rat striatal slices

Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic transmission through inhibition of dopamine uptake and enhanced release of the transmitter. We evaluated the changes in the inhibition of uptake and the release of striatal [3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200-250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were used. In the behavioral experiments the rats (N = 8 for each group) received FCF (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the duration of activity (sniffing, rearing and locomotion) was recorded for 120 min. The basal motor activity was higher (28.6 + 4.2 vs 8.4 + 3.5 s) after saline administration at 21:00 h than at 9:00 h. FCF at a sigle dose significantly enhanced the basal motor activity (38.3 + 4.5 vs 8.4 + 3.5 s) and increased the duration of exploratory activity (38.3 + 4.5 vs 32.1 + 4.6 s) during the light, but not the dark phase. Two other groups of rats (N = 6 for each group) were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine uptake and release assays. The inhibition of uptake and release of [3H]-dopamine were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the release properties of FCF undergo daily variation. These data suggest that the circadian time-dependent effects of FCF might be related to a higher susceptibility of dopamine presynaptic terminals to the action of FCF during the light phase which corresponds to the rats' resting period.

Effect of apomorphine on rat motor activity induced by fencamfamine and other indirect psychostimulant drugs

We evaluated the effects of low doses of apomorphine on the stimulant behavioral effects induced by amphetamine (2.5 mg/Kg), fencamfamine (6.0 mg/Kg) and cocaine (15,0 mg/Kg). Rats received 0.02 mg/Kg of apomorphine (sc) and 30 min later were injected with one of the stimulants.Motor activity including locomotion, rearing and sniffing was quantified in the animals home cages for 60 min at 15-min intervals. All stimulant drugs induced hyperactivity. When apomorphine was administered before cocaine, but not when administered before fencmfamine or amphetamine, distinctive changes occurred. The behavioral pattern resulting from high stimulation was replaced by that related to low stimulation, suggesting that apomorphine induces a transfer in the predominant behvior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occured when apomorphine was administered before amphetamine, the fencamfamine group showed intermediate alterations (nonsignificant changes in sniffing but a significant increase in rearing behavior). These results are discussed in terms of the different mechanisms of presynaptic action of the drugs studied

The behavioral sensitization induced by fencamfamine is not related to plasma drug levels

Fencamfamine (FCF) is a CNS stimulant that facilitates central dopaminergic transmission primarily though blockade of dopamine uptake. In the present study we evaluated the relationship between plasma FCF concentration and behavioral sensitization effect. Adult male Wistar rats (250-300 g) received FCF (10 mg/Kg, ip) or saline oince or daily for 10 consecutive days (N = 10 for each group). Blood samples were collected 30 min after injections and plasma FCF was measured by gas chromatography using an electron capture detector. FCF treatment enhanced sniffing duration (16.8 ñ 0.8 vs 26.6 ñ 0.9s) and decreased rearing behavior (8.2 ñ 0.8 vs 3.7 ñ 0.6s) when days 1 and 10 of drug administration were compared. Comparison of pair of means by the Student t-test did not show significant differences in plasma FCF concentration (390 ñ 40 vs 420 ñ 11 ng/ml) when blood samples were collected 30 min after acute FCF administration or after daily administration of 10 mg/Kg for 10 days. In conclusion, the behavioral sensitization to FCF could not be correlated with plasma drug levels, and changes in the activity of dopaminergic systems should be considered to explain the sensitization to the effect of FCF

Daily variation in plasma concentration of fencamfamine and striatal dopamine receptors in rats

Fencamfamine (FCF) is a psychostimulant drug classified as an indirect dopamine agonist. In the present study we evaluated the daily variation in plasma FCF concentration and in striatal dopamine receptors. Adult male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark cycle (lights on at 07:00 h) were used. Rats received FCF (10.0 mg/kg, ip) at 09:00, 15:00, 21:00 or 03:00 h and blood samples were collected 30 (N = 6) or 60 (N = 6) min after the injections. Plasma FCF was measured by gas chromatography using an electron capture detector. Two-way ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest value was obtained following injection at 21:00 h. Moreover, at 15:00, 21:00 and 03:00 h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of rats (N = 6) were decapitated at 09:00 or 21:00 h and the striata were dissected for the binding assays. The Bmax for [3H]-spiroperidol binding to striatal membranes was higher at 21:00 h, without changes in affinity constant (Kd). In conclusion, plasma FCF levels and dopamine receptors undergo daily variation, a phenomenon that should be considered to explain the circadian time-dependent effects of FCF

Effect of fencamfamine on avoidance performances of rats

The effects of fencamfamine (1.0 and 5.0 mg/kg, ip single dose) on an inhibitory task were studied in rats (N=15 per group).Post-training treatment with fencamfamine (1.0 mg/kg) significantly increased avoidance latency from 23 ñ 3 to 146 ñ 28 and 170 ñ 33 s for training day 1 and day 7, respectively, indicating an enhacement of retention.However, retention was significantly reduced with a high dose of fencamfamine (5.0 mg/kg). These results demonstrate that fencamfamine caused a reproducible dose-related increase and reduction in avoidance latency

Avaliaçäo do potencial de dependência da fencamfamina em alcoólatras recém-tratados: estudo duplo-cego e cruzado com placebo

Os autores apresentaram os resultados de avaliaçäo do possível uso abusivo da fencamfamina por 40 alcoólatras crônicos recém-internados. O estudo obedeceu metodologia duplo-cego cruzado, envolvendo três grypos (fencamfamina, cafeína e placebo), seguido de escolha forçada. A capacidade dessas drogas de estimular e de ocasionar efeitos subjetivos positivos foi avaliada através da auto-administraçäo, da preferência da droga, da escala "Profile of Mood States" (POMS) e das subescalas "Addiction Research Center Inventory" (ARCI): "Amphetamine e Significant Scale", Marginally Significant Scale", "BG Scale 12", "PCAG-4 Scale 452", MBG-10 Scale 453"e "LSD-21 Scale 454. O consumo médio diário foi similar para as três drogas. A fencamfamina e o placebo foram as drogas preferidas, tendo sido escolhidas em proporçöes semelhantes. As drogas utilizadas näo provocaram alteraçöes subjetivbas características de psicoatividade passíveis de detecçäo através da escala POMS ou pelas subescalas ARCI. Considerando-se a populaçäo estudada, doses e escalas utilizadas, näo se percebeu sinal algum de açäo estimulante ou efeito euforizante

On the mechanism which mediates the effects of long-term administration of fencamfamine in rats

This study analyzes the changes in the sensitivity of striatal dopaminergic (DA) receptors to apomorphine following withdrawal from long-term treatment with fencamfamine (10 mg/kg, for 40 days). Fencamfamine treatment decreased (34.8 + or - 3.2 vs 25.8 + or - 2.8,P<0.05) the stereotyped behavior induced by apomorfhine (2.0 mg/kg, sc), but potentiated the effect of apomorphine (0.02 mg/kg, sc) in reducing the striatal levels of homovanillic acid (HVA) (0.41 + or - 0.02 micron g/g vs 0.31 + or - 0.03 microng/g, P<0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 + or - 0.04 microng/g vs 0.34 + or - 0.03 microng/g, P<0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine

Psychostimulant effects of fencamfamine in healthy volunteers

The effects of fencamfamine (25 and 50 mg po) were studied on acute psychophysiological and psychomotor performance in six healthy male volunteers. Stimulant effects, such as greater increases of critical flicker-fusion thereshold, heart rate, blood pressure and stimulation assessed by self-rating, were more pronounced with the higher dose of fencamfamine. Paradoxical sedative effects were obrained with the 25 mg dose. Fencamfamine should not be considered only as an energizing agent, but also as an agent having a psychostimulant profile of effects

Alteraçöes na atividade do sistema dopaminérgico estriatal durante e após a administraçäo prolongada de fencanfamina e anfetamina / Changes in the activity of striatal dopaminergic system during and after long-term administration of fencamfamine and amphetamine

As alteraçöes na atividade do sistema dopaminérgico estriatal durante e após a administraçäo prolongada de fencanfamina (FCF) e anfetamina (ANF) foram estudadas em ratos machos. Durante o tratamento com FCF foi observado aumento gradual no comportamento de cheirar e uma tendência em diminuir o levantar estereotipado. Näo foram observadas alteraçöes significativas no comportamento de locomoçäo dos animais tratados com FCF e ANF. Após 72 horas da retirada dos fármacos, a administraçäo prolongada de ANF e FCF alterou os efeitos neuroquímicos da apomorfina (APO) reduzindo os níveis do ácido dihidroxifenilacético (DOPAC) no corpo estriado, quando comparado ao grupo tratado com salina + APO. Essas alteraçöes podem ser responsáveis pela eventual tolerância ou sensibilizaçäo da estereotipia induzida por esses fármacos

Prováveis mecanismos de açäo de estimulantes tipo anfetamínicos sobre o sistema nervoso central / Probable mechanisms of action of amphetamine type stimulants on the central nervous system

Nesta revisäo säo apresentados os prováveis mecanismos de açäo das drogas psicoestimulantes, tendo como padräo a anfetamina. Säo revistos também resultados obtidos com os estudos sobre a fencanfamina (Reactivan), um estimulante utilizado abusivamente em nosso meio. A administraçäo dessas drogas aumenta a liberaçäo de dopamina de ambos os reservatórios celulares de armazenamento. Estes efeitos säo dose-dependentes e multifásicos e, portanto, de difícil interpretaçäo em termos funcionais da transmissäo dopaminérgica

Venda de medicamentos sem receita médica nas farmácias da cidade de Säo Paulo / Sale of drugs without medical prescription in pharmacies of the city of Säo Paulo

Estudantes de medicina dirigiram-se a farmácias da cidade de Säo Paulo simulando uma queixa e solicitando um medicamento para o primeiro balconista a atendê-los. As queixas referiam-se a: "estar muito nervoso", "estar com muito sono", "estar com insônia", "querer emagrecer" e "alcoolismo em pessoa da família". Em 98 das 101 farmácias visitadas, o primeiro balconista a atender vendeu um medicamento; 75% dos medicamentos eram produtos farmacêuticos com faixa vermelha que deveriam ser vendidos somente com prescriçäo médica. Para as queixas "muito nervoso" e "insônia" os medicamentos vendidos, respectivamente em 90 e 100% das visitas, foram em sua imensa maioria (79%) os ansiolíticos antidistônicos, contendo 5 a 7mg de diazepam, 1mg de lorazepam, ou 15mg de oxazepam. Para a queixa de "muito sono", mais da metade dos estudantes comprou medicamentos à base de fencanfamina (ou norcanfano), uma droga com açäo tipo anfetamínica. Medicamentos à base de mazindol, droga tipo anfetamínica, e que exigem notificaçäo de receita B (bloco azul) foram livremente vendidos a 57% dos estudantes, que compraram produtos farmacêuticos indicados pelo balconista para "emagrecer". Para 71% dos estudantes que expuseram a queixa "alcoolismo na família" os balconistas venderam produtos à base de dissulfiram. Dos 98 estudantes que compraram medicamentos, apenas 17 foram alertados sobre possíveis efeitos colaterais, freqüentemente de maneira incompleta ou incorreta