Applications of nuclear magnetic resonance spectroscopy in the screening of new psychoactive substances / 中国药科大学学报

@#GC-MS and LC-MS are the main techniques used for the structural identification of new psychoactive substances at present. However, they are hard to give accurate structure information because of the hardly available corresponding reference standards and the quickly changing status of these compounds. This leads tremendous obstacle on the rapid identification of new psychoactive substances. Nuclear magnetic resonance spectroscopy is one of the most effective methods for structures identification. Therefore, NMR is especially suitable for the analysis and identification of new psychoactive substances even with rapid structural changes. This article summarizes the NMR applications for the structural analysis of new psychoactive substances including synthetic cannabinoids, synthetic cathinones, piperazines, phenethylamines, ketamine & phencyclidine-type substances, and fentanyls. It is found that the NMR signals of the main frame structure of each kind of the new psychoactive substances are basically the same. Hence, these frame structure NMR signals can provide scientific evidence for the rapid identification of new psychoactive substances. This article also look ahead the prospect for the application of LC-NMR and DOSY in new psychoactive substances, which provides new ideas for the screening of new psychoactive substances.

Sobre a analgesia pós-operatória da morfina, cetamina ou da associação em cadelas submetidas à ovariossalpingohisterectomia eletiva / About post operatory analgesia of morphine, ketamine or their combination in bitches undergoing elective ovariohysterectomy

Este estudo objetivou avaliar a eficácia analgésica da morfina e cetamina, isoladas ou associadas, para tratar a dor pós-operatória de cadelas submetidas à ovariossalpingohisterectomia (OSH) eletiva. Foram utilizadas 24 cadelas saudáveis, de raças variadas, idade de 27±17 meses e massa corpórea de 11±8,5kg. Os animais foram separados de forma igualitária e aleatória em três grupos: GM - morfina 0,5mg kg-1; GK - cetamina 2,5mg kg-1 ou GKM - morfina 0,5mg kg-1, associada à cetamina 2,5mg kg-1 . Os fármacos foram administrados por via intramuscular (IM) imediatamente após a indução anestésica. A dor foi avaliada por meio de escala analógica visual (EAV) e de Glasgow modificada (EGM) e o grau de sedação pela escala de Dobbins, duas horas antes do procedimento cirúrgico (basal), 1, 2, 4, 8, 12 e 24 horas após a extubação (M1 a M24). Quando a pontuação da EGM era acima de 33% do valor total da avaliação, realizava-se resgates analgésicos com 1,0mg kg-1 de morfina e, após 40 minutos deste resgate, caso não fosse suficiente, 0,2mg kg-1 de meloxicam. Os dados não paramétricos foram submetidos ao teste de Friedman ou Kruskal-Wallis, seguidos do teste de Dunn. Para os paramétricos, foi empregada análise de variância unidirecional ANOVA, seguida do teste de Tukey (P<0,05). Não houve diferenças significativas entre os grupos para os escores de dor, exceto para EGM, na qual os valores no GM foram superiores ao GKM 1h após a extubação. O número de resgates analgésicos foi significativamente superior no GM (todos os animais, com 11 resgates no total), em relação ao GKM (3) e GK (um animal por duas vezes). A administração pré-incisional de cetamina foi mais efetiva do que a oferecida pela morfina e, dessa maneira, a cetamina pode ser empregada para analgesia preemptiva em cadelas submetidas à OSH, entretanto, pode ser necessária analgesia de resgate.

This study aimed to evaluate the post operative analgesic effects of morphine or ketamine alone or their combination in 24 healthy bitches, weighing 11.01±8.69kg and aging 27±17 months, submitted to elective ovariohysterectomy. The animals were distributed to one of the three treatments after the anaesthetic induction: morphine (GM, n=8, 0.5mg kg-1 IM), ketamine (GK, n=8, 2.5mg kg-1 IM) or ketamine combined to morphine (GKM) using the same doses previously described. Sedation score and pain assessment were performed blindly two hours before surgery and at 1, 2, 4, 8, 12, and 24 hours after extubation, using the Dobbins scale (sedation) and visual analogue scale (pain) and Glasgow modified pain scale (GMPS). Rescue analgesia was performed with 1.0mg kg-1 of morphine and if not sufficient, followed by 0.2mg kg-1 of meloxicam, both IM, when the GMPS reached above 33% of the total score. Non parametric data were analyzed using Friedman´s test followed by Dunn´s test for differences in time. Kruskal-Wallis´ test followed by Dunn´s test were used to investigate differences in the number of analgesic rescues and among groups at each time. Parametric data were evaluated by ANOVA followed by Tukey's test (P<0.05). Except for GMPS, where the values of GM were greater than for GKM at 1h post-extubation, there were no other differences among groups. The number of rescue analgesia was greater in GM (11 in total; twice in 3 animals,) when compared to GKM (3; twice in 1 animal) and GK (2; twice in 1 animal). Analgesia provided by pre-incisional ketamine was more effective when compared to morphine. According to that, ketamine alone may be used as a preemptive analgesic in bitches undergoing ovariohysterectomy; however, rescue analgesia may be necessary.

Research on the change of negative symptoms in PCP-induced schizophrenia rat model / 中华行为医学与脑科学杂志

Objective To study the changes of negative symptoms in PCP-induced schizophrenia rat model.Methods Thirty newborn female SD rats randomly divided into control group,PCP-week 6 group and PCP-week 10 group( n=10 in each group).Perinatal rat treated with PCP ( 10 mg/kg) on postnatal days 7,9 and 11(10 mg/kg,ip),and sucorse intalce test(SIT),forced swimming test(FST) and resident-intruder test(RIT) were used to test the emotional and negative symptoms.Results In the SIT,there was no difference between control and PCP groups (con:(28.24 ±0.86) ml/kg; week 6:(26.57 ± 1.01 ) ml/kg; week 10:(27.98 ±0.99) ml/kg,F =12.35,P ＞ 0.05 ).In the FST,PCP model rats showed longer still time ( con:(39.32 ± 1.98 ) s ; week 6:(52.39 ± 1.66)s,week 10:(55.56 ± 1.49)s,F=3.99,P＜ 0.05 ).In the RIT,PCP models rats showed less explore time ( (40.31 ± 13.56)s vs (63.90 ± 13.12)s,(43.65 ±12.86 )s vs (65.18 ± 15.12)s,P ＜ 0.05 ) and more escape time ((19.33±2.26) s vs (9.26 ± 1.32) s,(17.79 ±2.99) s vs (9.38 ± 1.36) s,P＜ 0.05).Conclusion Perinatal PCP injection can induce the long-lasting negative-symptoms changes.

Effects of the Antioxidant Sulforaphane on Hyperlocomotion and Prepulse Inhibition Deficits in Mice after Phencyclidine Administration

OBJECTIVE: Accumulating evidence suggests that oxidative stress plays a role in the pathophysiology of schizophrenia and that the potent antioxidants may be potential therapeutic drugs for schizophrenia. This study was undertaken to examine the effects of the potent antioxidant sulforaphane (SFN), found in cruciferous vegetables, on behavioral abnormalities (e.g., hyperlocomotion and prepulse inhibition [PPI] deficits) in mice after a single administration of the N-methyl-D-aspartate (NMDA)-receptor antagonist phencyclidine (PCP). METHODS: Effects of SFN (3, 10, and 30 mg/kg, intraperitoneally [i.p.]) on hyperlocomotion and PPI deficits in the adult male ddY mice after administration of PCP (3.0 mg/kg, subcutaneously [s.c.]) were examined. RESULTS: Administration of SFN (30 mg/kg, intraperitoneally [i.p.]), but not low doses (3 and 10 mg/kg, i.p.), significantly attenuated hyperlocomotion in mice after PCP administration (3.0 mg/kg, subcutaneously [s.c.]). Furthermore, administration of SFN (3, 10, and 30 mg/kg, i.p.) attenuated the PPI deficits in mice after PCP administration (3.0 mg/kg, s.c.) in a dose-dependent manner. CONCLUSION: These results suggest that SFN has antipsychotic activity in an animal model of schizophrenia. Therefore, it is likely that SFN may be a potential therapeutic drug for schizophrenia.

Iptakalim Preferentially Decreases Nicotine-induced Hyperlocomotion in Phencyclidine-sensitized Rats: A Potential Dual Action against Nicotine Addiction and Psychosis

OBJECTIVE: Iptakalim is a putative ATP-sensitive potassium (KATP) channel opener. It is also a novel nicotinic acetylcholine receptor (nAChR) blocker and can antagonize nicotine-induced increase in dopamine release in the nucleus accumbens. Our recent work also shows that iptakalim exhibits a clozapine-like atypical antipsychotic profile, indicating that iptakalim may possess a dual action against nicotine addiction and schizophrenia. METHODS: The present study examined the potential therapeutic effects of iptakalim on nicotine use in schizophrenia. We created an animal model of comorbidity of nicotine addiction and schizophrenia by injecting male Sprague-Dawley rats with nicotine (0.40 mg/kg, subcutaneously[sc]) or saline, in combination with phencyclidine (PCP, 3.0 mg/kg, sc) or saline daily for 14 consecutive days. RESULTS: During the PCP/nicotine sensitization phase, PCP and nicotine independently increased motor activity over time. PCP also disrupted prepulse inhibition (PPI) of acoustic startle response. Acute nicotine treatment attenuated the PCP-induced hyperlocomotion and PCP-induced disruption of PPI, whereas repeated nicotine treatment potentiated these effects. Importantly, pretreatment with iptakalim (10-20 mg/kg, intraperitoneally) reduced nicotine-induced hyperlocomotion in a dose-dependent fashion. This reduction effect was highly selective: it was more effective in rats previously sensitized to the combination of PCP and nicotine, but less effective in rats sensitized to saline, nicotine alone or PCP alone. CONCLUSION: To the extent that the combined nicotine and PCP sensitization mimics comorbid nicotine addiction in schizophrenia, the preferential inhibitory effect of iptakalim on nicotine-induced hyperlocomotion suggests that iptakalim may be a potential useful drug for the treatment nicotine abuse in schizophrenia.

Rapid Changes in D1 and D2 Dopamine Receptor Binding in Striatal Subregions after a Single Dose of Phencyclidine

OBJECTIVE: In humans, a single exposure to phencyclidine (PCP) can induce a schizophrenia-like psychosis which can persist for up to two weeks. In rats, an acute dose of PCP increases dopaminergic activity and causes changes in dopamine related behaviours some of which are sexually dimorphic. To better understand the effects of PCP on dopamine receptor adaptations in the short term we examined dopamine D1-like receptors (D1R) and D2-like receptors (D2R) in the mesolimbic and nigrostriatal dopamine pathways, 4 hours after exposure to PCP in female rats. METHODS: Animals received a single dose of 40 mg/kg PCP and were sacrificed 4 hours later. In vitro autoradiography was carried out using [3H] SCH 23390 and [3H] raclopride that target D1R and D2R respectively, in cryostat brain sections. RESULTS: Two way analysis of variance (ANOVA), revealed an overall effect of PCP treatment (F [1,63]=9.065; p=0.004) on D1R binding with an 18% decrease (p<0.01) in binding in the medial caudate putamen. PCP treatment also had an overall effect on D2R binding (F [1,47]=5.450; p=0.024) and a trend for an increase in D2R binding across all the brain regions examined. CONCLUSION: These results suggest opposing D1R and D2R adaptations in striatal subregions of female rats following acute exposure to PCP that may occur through indirect mechanisms.

Effects of a New Antipsychotic Drug (YKP1447) on Impaired Prepulse Inhibition Induced by Apomorphine and Phencyclidine in Rats / 대한정신약물학회지

OBJECTIVE: Schizophrenia, a devastating mental disorder, displays a wide range of cognitive impairments including attentional impairment. Prepulse inhibition (PPI), in which a startle response to a loud acoustic noise is reduced by a preceding auditory stimulus of a lower intensity, is impaired in schizophrenic patients and rats injected with apomorphine (APO) or phencyclidine (PCP) mimicking attentional deficits in schizophrenics. Here we examined therapeutic efficacy of a newly developed atypical antipsychotic compound (YKP1447;YKP) on PPI impairment induced by various doses of APO and PCP. METHODS: This study was composed of 3 experiments. YKP (0.5-15 mg/kg) or vehicle (VEH) was administered 15 min before the injection of APO (0.5 mg/kg, Exp1) or PCP (2.0 mg/kg, Exp2:1.5 mg/kg, Exp3). They were then tested for PPI in which a mix of startle stimulus and prepulse was presented. RESULTS: APO or PCP treatment effectively impaired PPI in tested animals (VEH/APO or VEH/PCP). Impaired PPI in APO group was reversed in animals that were pretreated with YKP (5-10 mg/kg) (Exp1). However YKP treatment was not effective in PCP group (Exp2-3). CONCLUSION: High concentration of YKP pretreatment had antipsychotic effect on APO-induced impairment in attentional function suggesting that the compound could potentially be used to treat cognitive impairment due to increased dopaminergic receptorbinding.

PROTECTIVE EFFECT OF PHENCYCLIDINE ON ACUTE CEREBRAL ISCHEMIA OF RABBIT-ANALYSIS OF BETA- ENDORPHIN IMMUNOREACTIVITY IN CEREBROSPINAL FLUID / 中国药理学通报

Acute cerebral ischemia and reperfusion injury of rabbits was produced by permanently occluding the vertebral arteries and temporarily clamping the common carotid arteries for 30 min. Beta-endorphin immunoreactive substance ( ir beta-endorphin ) content were measured in cerebrospinal fluid at pre-ischemia and after ischemia and reperfusion stages. In control group, the content of ir beta-endorphin significantly increased (1.01?0.52 mg/L, P