Psychostimulants
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Press and internet reports mention abuse of nootropic drug piracetam (PIR) in combination with psychostimulants methamphetamine (MET) or 4-methylenedioxymethamphetamine (MDMA). These combinations are believed to produce more profound desirable effects, while decreasing hangover. However, there is a lack of valid experimental studies on such drug-drug interactions in the scientific literature available. Our hypothesis proposes that a functional interaction exists between PIR and amphetamine psychostimulants (MET and MDMA) which can potentiate psychostimulant behavioural effects. Our hypothesis is supported by the results of our pilot experiment testing acute effects of drugs given to mice intraperitoneally (Vehicle, n=12; MET 2.5mg/kg, n=10; MDMA 2.5mg/kg, n=11; PIR 300 mg/kg, n=12; PIR+MET, n=12; PIR+MDMA, n=11) in the Open Field Test (Actitrack, Panlab, Spain). PIR given alone caused no significant changes in mouse locomotor/exploratory behaviour, whereas the same dose combined with either MET or MDMA significantly enhanced their stimulatory effects. Different possible neurobiological mechanism underlying drug-drug interaction of PIR with MET or MDMA are discussed, as modulation of dopaminergic, glutamatergic or cholinergic brain systems. However, the interaction with membrane phospholipids seems as the most plausible mechanism explaining PIR action on activities of neurotransmitter systems. Despite that our behavioural experiment cannot serve for explanation of the pharmacological mechanisms of these functional interactions, it shows that PIR effects can increase behavioural stimulation of amphetamine drugs. Thus, the reported combining of PIR with MET or MDMA by human abusers is not perhaps a coincidental phenomenon and may be based on existing PIR potential to intensify acute psychostimulant effects of these drugs of abuse.
- MeSH
- amfetaminy aplikace a dávkování MeSH
- chování zvířat účinky léků fyziologie MeSH
- kombinovaná farmakoterapie MeSH
- myši MeSH
- neuroprotektivní látky aplikace a dávkování MeSH
- piracetam aplikace a dávkování MeSH
- stimulanty centrálního nervového systému aplikace a dávkování MeSH
- synergismus léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Psychostimulants are known to have a huge impact on different forms of social behaviour. The aim of the present study was to compare the effects of three different psychostimulants [amphetamine, cocaine and 3,4 methylenedimethoxyamphetamine (MDMA)] on social interaction (SI) in adult male rats. The SI test was performed in a familiar arena and under low-stress environmental conditions. Experimental animals received amphetamine (0.5, 1.0, 1.5 mg/kg), cocaine (0.5, 1.0, 1.5, 2.5, 5.0, 10.0 mg/kg) or MDMA (2.5, 5.0, 10 mg/kg) and control animals received saline (1 ml/kg) 45 min before the SI test. Time spent in SI (individual patterns of social behaviour) and nonsocial activities (locomotion and rearing) were video recorded and then analysed offline, with the following results: (a) all doses of amphetamine decreased SI. Specifically, all doses of amphetamine decreased mutual sniffing, and the higher doses also decreased allo-grooming and following behaviours. (b) The higher doses of cocaine decreased SI, especially mutual sniffing, allo-grooming and climbing over. Cocaine at the dose of 5.0 mg/kg increased genital investigation compared with lower doses. (c) All doses of MDMA decreased mutual sniffing and climbing over; the two higher doses decreased allo-grooming behaviour, and only the highest dose decreased following. The two higher doses of amphetamine and all the doses of MDMA increased locomotion and rearing; cocaine did not affect locomotion, but increased rearing at higher doses. In conclusion, the results confirm the well-known finding that psychostimulants suppress SI, but also show novel differences in the effects of psychostimulants on specific patterns of SI.
- MeSH
- amfetamin farmakologie MeSH
- chování zvířat účinky léků MeSH
- interpersonální vztahy * MeSH
- kokain farmakologie MeSH
- krysa rodu rattus MeSH
- lokomoce účinky léků MeSH
- N-methyl-3,4-methylendioxyamfetamin farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Repeated administration of psychostimulants and other dependence-producing substances induces a substantial increase in behavioural responses, a phenomenon termed as behavioural sensitization. An increased response to the tested drug elicited by previous repeated administration of a different drug is called cross-sensitization. Behavioural sensitization is considered to be a relapse trigger in dependent subjects and animals sensitized by repeated administration of drugs of abuse, thus being considered a suitable model of craving, which is one of the very characteristic features of substance addiction. It has been described that apart from other actions, drugs of abuse exert their effect on the central nervous system by affecting glutamatergic transmissions, particularly via N-methyl-d-aspartate (NMDA) receptors. Thus, this review presents a brief overview of the impact of inhibition of the NMDA receptor system on sensitization, reflecting particularly on behavioural sensitization to psychostimulants. The text combines up-to-date information with time-proven facts and also compares data from the literature with the authors׳ recent findings concerning this topic.
Prenatal exposure to methamphetamine (METH) increases nociceptive sensitivity in adult rats. As the strong analgesics have high abuse potential and drugs of abuse are known to have analgesic properties, the aim was to study analgesic effect of different psychostimulants in control and prenatally METHexposed rats. Latencies of withdrawal reflexes of hind limbs and the tail on thermal nociceptive stimuli were repeatedly measured in 15-min intervals after the application of 5 mg/kg s.c. of amphetamine (AMPH), methamphetamine (METH), cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA) or morphine (MOR). In all groups, AMPH induced on hind limbs stronger analgesia than METH and MDMA whereas COC and MOR were practically without any effect. On the tail, effect of AMPH did not differ from that of MOR. All psychostimulants increased defecation in comparison with MOR and in all groups the number of defecation boluses positively correlated with analgesia of the hind limbs. We did not confirm that prenatal exposure to METH makes adult rats more sensitive either to same drug or to other psychostimulants. The different analgesic potencies of psychostimulants and MOR at different body sites indicate the possible existence of a somatotopic organization of pain inhibition, which is controlled by different mechanisms.
- MeSH
- amfetamin farmakologie škodlivé účinky MeSH
- chování zvířat účinky léků MeSH
- kokain farmakokinetika škodlivé účinky MeSH
- krysa rodu rattus MeSH
- methamfetamin farmakologie škodlivé účinky MeSH
- morfin farmakologie škodlivé účinky MeSH
- N-methyl-3,4-methylendioxyamfetamin farmakologie škodlivé účinky MeSH
- narkotika * farmakologie škodlivé účinky MeSH
- stimulanty centrálního nervového systému * farmakologie škodlivé účinky MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * metabolismus patofyziologie psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Karfedon je fenyl-derivátem nootropního léku piracetamu (NOOTROPIL) a je účinný při zvyšování fyzické vytrvalosti a odolnosti proti chladu a používá se k léčbě ztráty paměti. Byl vyvinut v Rusku jako stimulans, aby kosmonauti na dlouhých misích zůstávali bdělí a neusínali, a občas je používán v Rusku pro různé typy neurologických onemocnění. Dobře známým se stal před pár lety, když jej jedna firma z Kalifornie začala prodávat na Internetu jako doplněk stravy a poté byla řada sportovců vyloučena z olympijských her pro jeho nezákonné použití. Karfedon významně aktivuje operantní chování (podmiňování), odstraňuje psychodepresivní účinky diazepamu, zlepšuje postrotační nystagmus a brání rozvoji retrográdní amnézie. Na rozdíl od piracetamu, karfedon vykazuje určitý antikonvulzivní účinek. Je-li podán ve vysokých dávkách, má depresivní účinky. Je také známo, že zvyšuje fyzickou kondici a navozuje větší toleranci k chladu. V důsledku toho se objevil na seznamu zakázaných látek, vydaném Světovou antidopingovou agenturou.
Carphedon is a phenyl derivative of the nootropic drug piracetam (NOOTROPIL) which is effective in increasing physical enduranc e and cold resistance, and is used for amnesia treatment. It was developed in Russia as a stimulant to keep astronauts awake on l ong missions, and occasionally used in Russia as a nootropic prescription for various types of neurological diseases. It became wel l known a couple years ago when a leading nootropic supplier in California started selling it on the Internet as a supplement and a bun ch of athletes got kicked out of the Olympics for illegal using it. Carphedon was found to activate the operant behavior more powerfu lly, to remove psychodepressant effects of diazepam, to inhibit post-rotational nystagmus, and to prevent the development of retrogr ade amnesia. Unlike piracetam, carphedon exhibits a specific anticonvulsant action. When given in high doses, produces psychodepres sant effects. It is also claimed to increase physical stamina and provide improved tolerance to cold. As a result, it appears on the lists of banned substances issued by the World Anti-Doping Agency.
- Klíčová slova
- stimulans, 2-(4-fenyl-2-oxopyrrolidin-1-yl)acetamid, fenotropil,
- MeSH
- amfetaminy farmakologie terapeutické užití MeSH
- doping ve sportu MeSH
- hodnocení léčiv MeSH
- látky zvyšující výkon farmakologie MeSH
- lidé MeSH
- nootropní látky farmakologie terapeutické užití MeSH
- piracetam analogy a deriváty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
