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1.
PLoS One ; 19(3): e0294999, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483938

RESUMO

Allium Cepa Linn. (Onions) has extensively been used in traditional medicine, is one of the important Allium species regularly used in our daily diet, and has been the source of robust phenolic compounds. The current study is intended to evaluate the fecundity-enhancing effect of A. Cepa on the reproductive performance of two successive generations of rats; F0 and F1. A. Cepa extract was initially tested for in vitro antioxidant assay via DPPH and ROS, followed by in vivo toxicity testing. In the fecundity assessment, eighteen pairs of male and female rats (n = 36, 1:1, F0 generation) were divided into three groups and dosed with 75mg/kg and 150 mg/kg daily of A. Cepa extract and saline respectively, up to pre-cohabitation, cohabitation, gestation and lactation period. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Various parameters like Hematological, Hormonal (FSH, LH, Testosterone, estradiol), antioxidant markers (SOD, Glutathione peroxidase) and lipid profile of F0 and F1 generations were assessed with evaluation of histopathology of male and female organs. Ethanolic extract of A. Cepa showed the greatest antioxidant potential in DPPH and ROS methods. The continued exposure of the F0 and F1 generations to A. Cepa extract did not affect body weight, fertility index, litter size, and survival index. However, semen pH, sperm motility, sperm count, sperm viability, and semen volume were significantly improved in both generations. We have found pronounced fecundity outcomes in both genders of F0 and F1 generations with A. Cepa 150mg/kg/day extract as compared to control. Results showed that A. Cepa significantly increased (P < 0.05) hemoglobin, follicular stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone and glutathione peroxidase activities, while total lipid, LDL, and cholesterol were significantly decreased (P < 0.05) in both generations. Histology of both generations of animals reveals enhanced spermatogenesis and enhanced folliculogenesis with improved architecture. Altogether, the present results suggest that A. Cepa extract improved fecundity in both male and female rats by improving hormonal activities and oxidative stress.


Assuntos
Antioxidantes , Cebolas , Ratos , Masculino , Feminino , Animais , Espécies Reativas de Oxigênio/farmacologia , Antioxidantes/farmacologia , Motilidade dos Espermatozoides , Sementes , Reprodução , Fertilidade , Peso Corporal , Testosterona , Hormônio Luteinizante/farmacologia , Hormônio Foliculoestimulante/farmacologia , Glutationa Peroxidase , Lipídeos/farmacologia
2.
Pak J Pharm Sci ; 36(5(Special)): 1609-1618, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38008959

RESUMO

Melissa officinalis and Panax ginseng extracts were investigated to determine combinatorial effects on cognitive behaviors' of albino-rats. The study was prospective-experimental; lasted from June-2022 to March-2023. Learning and memory measurements were done by animal-models. Data analyzed by 22nd version of SPSS. In Passive-avoidance-test both doses of Melissa officinalis and Panax ginseng (100/100mg/kg and 200/200mg/kg) showed significant differences in number of acquisition-trial between groups (p<0.001); drug treated groups showed longer latency-period compared to control and scopolamine (p<0.001). In time-spent-in-dark-chamber treated groups spent less-time in dark-chamber as compared to control and scopolamine (p<0.001). In Morris-water-maze-task treatment groups (100/100mg/kg and 200/200mg/kg) showed significant (p<0.001) decrease in escape-latency compared with control and scopolamine. Spatial-memory-probe showed significant interaction between drugs and days (p<0.001); time-spent in platform region is significantly increased (p<0.001) in both treatment groups compared with control and scopolamine. 8-arm-radial-maze-test showed the significant increase (p<0.05) in total number of correct responses in treatment groups (100/100mg/kg and 200/200mg/kg) compared to control and scopolamine. In-vitro studies revealed acetyl-choline-esterase inhibition by 36.40% from Melissa officinalis and Panax ginseng combination. Study concluded that combination of M. officinalis and P. ginseng extracts may significantly improve the effects on memory and cognition.


Assuntos
Melissa , Panax , Animais , Estudos Prospectivos , Escopolamina/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Aprendizagem em Labirinto , Cognição , Transtornos da Memória/tratamento farmacológico
3.
ACS Pharmacol Transl Sci ; 6(10): 1357-1372, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37854618

RESUMO

PURPOSE: Chronic stressful situations result in altered monoaminergic activity of neurotransmitters, resulting in various conditions characterized by deficits in learning, memory and attention. Stimulant effects can be visualized in terms of increased cognitive abilities through enhancement of dopamine (DA) release. METHOD: This study examined cognitive responses and brain DA and 5-hydroxytryptamine (5HT) levels after prolonged methylphenidate (MPH) and modafinil administration, to demonstrate their effect on stress-induced cognitive deficits in rats. Effects on cognition were evaluated by passive avoidance and water maze tests. Furthermore brain levels of DA, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5HT and 5-hydroxyindoleacetic acid (5HIAA) were analyzed by high-performance liquid chromatography coupled with electrochemical detection. RESULTS: We found that both MPH and modafinil improved cognition in both restrained and unrestrained rats, as examined through water maze and passive avoidance tests. Furthermore, these substance were associated with increased brain DA and 5-HT levels. Notabily, we observed decrease in DOPAC and HVA levels, while 5-HIAA levels exhibited a slight increase. CONCLUSIONS: The prevention of stress-induced cognitive deficits by MPH and modafinil could be elucidated through the interaction between 5HT and DA in regulating cognitive function.

4.
Pak J Pharm Sci ; 36(2): 467-476, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37530154

RESUMO

High levels of reactive oxygen species (ROS) in the body and diabetes are key factors for the development of hypercholesteremia and related neuropathic pains. Current study aimed to compare the antioxidant, antidiabetic and analgesic activities of aqueous methanolic extracts of C. viminalis L. and A. rosea L. leaves. HPLC method was used for phenolic content evaluation. Antioxidant capacity was determined by DPPH and analgesic activity was performed via acetic acid induced writhing reflex test. Whereas the antidiabetic activity was performed on Alloxan induced diabetes model. HPLC analysis indicated the presence of phenols in both extracts. Based on DPPH radical scavenging activity, C. viminalis and A.rosea L. both leaves extracts showed strong scavenging activity (IC50, 11.96±0.64lg/mL) and (IC50, 10.11±0.74lg/mL) respectively. Antidiabetic effect of C. viminalis L and A. rosea L. were also significant (p<0.05). Further biochemical analysis showed both leaves extracts significantly (P<0.05) reduces glucose, Low density lipid (LDL), triglycerides (TG), total cholesterol (TC) and urea while high density lipid (HDL) were improved. In writhing reflex test both extracts exhibited significant (P<0.01) analgesic activity which was comparable to Aspirin. In conclusion both C. viminalis L. and A. rosea L. leaves extracts displayed significant antioxidant, analgesic and antidiabetic activity.


Assuntos
Antioxidantes , Malvaceae , Antioxidantes/química , Hipoglicemiantes/química , Extratos Vegetais/química , Analgésicos/farmacologia , Lipídeos/análise , Folhas de Planta/química
5.
Pak J Pharm Sci ; 34(2): 499-506, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34275822

RESUMO

Natural oils are rich in polyunsaturated fatty acids (PUFs) like omega 3, omega 6 and other nutrients that boost physical and mental health. Traditionally these oils have been used to treat joint pain associated with several inflammatory conditions. In this study, we investigated the antioxidant and analgesic properties of the sesame oil (SO), fish oil (FO) and combination of these two oils (SO+FO). Different concentrations of the SO, FO and SO+FO combination 0.02-4mg/ml were used for assessing the free radical scavenging activity by DPPH method and the IC50 value was calculated. Acetic acid-induced abdominal writhing test, tail immersion and hot plate models were used to determined analgesic effect. Results showed that both oils were well tolerated as no signs of toxicity or death were noticed during the observational study period. SO+FO combination showed the best antioxidant properties as shown by DPPH assay. Similarly in analgesic models, SO and FO significantly reduced the number of abdominal contractions (p<0.05) however, SO+FO (1:1) exhibited highly significant results (p<0.001) in writhing reflex test. Furthermore, SO and FO both increased the reaction time on a hot plate as well as in tail flick test (p<0.05) whereas, SO+FO significantly increased reaction time (p<0.001) in hot plate and in tail flick test as compared to SO and FO single treatments. Conclusively, our results suggest that the combination of both oils (SO+FO) exhibited significant antioxidant and analgesic potential that it could be considered as one of the active combinations for relieving pain in adjunctive treatment for joint pain associated with rheumatoid arthritis.


Assuntos
Analgésicos/farmacologia , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Óleos de Peixe/farmacologia , Nociceptividade/efeitos dos fármacos , Óleo de Gergelim/farmacologia , Ácido Acético , Animais , Compostos de Bifenilo , Temperatura Alta , Indicadores e Reagentes , Injeções Intraperitoneais , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Picratos , Tempo de Reação/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Tubarões
6.
Pak J Pharm Sci ; 34(6): 2131-2139, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35034873

RESUMO

Methylphenidate (MPH) is a psychostimulant, beneficial in attention deficit hyperactivity disorder (ADHD). Previously it has been shown that MPH-induced locomotor sensitization could be attenuate by buspirone co administration however the effect of chronic MPH and co-administration of MPH-buspirone on biochemical and hematological parameters are unknown. This study is designed to investigate these parameters after long term administration of MPH, Buspirone and their combination in rats. 40 male Wister rats were divided in to 4 groups, and treated with saline, MPH (2mg/kg/day), Buspirone (10mg/kg/day) and MPH-Buspirone co-administration (2mg/kg/day ±10mg/kg/day; respectively) up to six weeks. Administration of MPH significantly increase blood glucose level in saline treated control rats, however co-administration of MPH-buspirone exhibited less effect on blood glucose levels. Serum creatinine levels significantly decreased in all treated groups as compared to control but highly significant results were seen with combination treatment. Co-administration of MPH-buspirone and buspirone treated rats exhibited increased cholesterol and hemoglobin values. All treated groups showed increased values of hematocrit, MCV, MCH and MCHC compared to control group. RBCs and WBC's count were decreased in all treated groups. The platelet count rose significantly by Buspirone and MPH-buspirone administration, while MPH showed decreased platelet count. Thus, results suggested that prolong co-administration of MPH-buspirone is safe and effective for ADHD patients by preventing adverse effects not only on behavioral but also on biochemical and hematological parameter.


Assuntos
Buspirona/toxicidade , Metilfenidato/toxicidade , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Buspirona/administração & dosagem , Colesterol/sangue , Creatinina/sangue , Esquema de Medicação , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemoglobinas/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Metilfenidato/administração & dosagem , Ratos Wistar , Fatores de Tempo
7.
Naunyn Schmiedebergs Arch Pharmacol ; 393(5): 785-795, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31853616

RESUMO

Stress increases the susceptibility of drug abuse and drugs of abuse impair behavioral tolerance. It has been shown that stress exposure enhances the sensitivity to the reinforcing properties of drugs, augments locomotor sensitization effects of drugs of abuse and impairs behavioral tolerance. Previously, it has been shown that long-term administration of psychostimulants (Methylphenidate and Modafinil) induced locomotor sensitization effect that was more pronounced after 13 days of drug administration and was greater at high dose. The present study is designed to investigate the relationship between restraint stress and psychostimulants (Methylphenidate and Modafinil) that induced sensitization. Methylphenidate (10 mg/kg/day twice a day), modafinil (75 mg/kg/day once daily), and saline (0.9% NaCl; 1 ml/kg/day) were administered orally to treated and control animals. Rats were exposed to immobilization stress for 30 days (until locomotor sensitization produced) to monitor any change in drug-induced behavioral sensitization. The motor activity was compared daily by using familiar environment of home cage and weekly by novel environment of open field. The results show that the methylphenidate and modafinil-induced locomotor sensitization is enhanced and impaired behavioral tolerance in repeated restrained rats. It shows that the psychostimulants like methylphenidate and modafinil produce greater locomotor sensitization in stressful environment, suggesting addictive effects of stress and psychostimulants (methylphenidate/modafinil) on dopaminergic neurotransmission. These finding may be helpful to develop potential pharmacotherapies for the patients with co-occurring depression and substance abuse/dependence disorder.


Assuntos
Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Locomoção/efeitos dos fármacos , Metilfenidato/farmacologia , Modafinila/farmacologia , Restrição Física , Estresse Psicológico/psicologia , Adaptação Psicológica , Animais , Modelos Animais de Doenças , Masculino , Atividade Motora/efeitos dos fármacos , Teste de Campo Aberto/efeitos dos fármacos , Ratos Sprague-Dawley , Reforço Psicológico , Estresse Psicológico/etiologia , Fatores de Tempo
8.
Pak J Pharm Sci ; 32(4(Supplementary)): 1861-1867, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680084

RESUMO

Drug utilization evaluation (DUE) is an arrangement of continuous, orderly, criteria-based assessment of medication utilizes to guarantee that medicines are utilized suitably. In the event that treatment is regarded to be improper, provider and patient intervention may be important to optimize therapeutic efficacy. In the present study drug utilization evaluation of Piperacillin/Tazobactam was carried out in prospective manner. A well structured data collection form was constructed to collect the related information regarding demographic, clinical use, indication, culture sensitivity criteria, outcomes of therapy, renal impairment cases of dose adjustments and appropriate use. Results of chi square indicated insignificant relationship between gender and as p value was found to be p=0.446 and 0.111 for use of drug alone and in combination. Similarly insignificant relationship between gender and use of drug in combination with other antibiotics as p value was found to be p=0.111. It was found that from 61-70 years (Therapeutic Effectiveness; n=12, 9.37%), (Therapeutic Failure; n=10, 45.45%) and mortality (n=1, 50%) were quite higher. The prescription pattern was in accordance with standard guidelines. Study indicated need to elevate prescribers to pursue generic prescribing and rationally utilize antibiotics to avert advancement of resistance at the level of hospital and community. These sorts of studies are valuable for acquiring data about medication utilize designs and for recognizing inconceivable expense of medicines.


Assuntos
Antibacterianos/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Quimioterapia Combinada/métodos , Uso de Medicamentos , Revisão de Uso de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Atenção Terciária à Saúde , Adulto Jovem
9.
Pak J Pharm Sci ; 32(2 (Supplementary)): 895-898, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103989

RESUMO

Methylphenidate is a psychostimulant used for the treatment of (ADHD) attention deficit hyperactivity syndrome in children and adults. After chronic administration it is known to produce behavioral disorders including anxiety. Previous studies demonstrated that co-administration of buspirone can reduce behavioral and cognitive adverse effects produced by methylphenidate. The aim of the present study is to measure the levels vanillylmandelic acid (VMA) excretion in urine following prolong administration of methylphenidate, buspirone and their combination. Samples of urine for the estimation of the urinary VMA excretion were collected from treated and control male Wistar rats. We found significant (P<0.01) raised urinary VMA excretion in methylphenidate group however significant (P<0.01) reduction in VMA levels were seen after buspirone co-administration. Excretion of VMA in urine would allow the monitoring of sympatho-adrenomedullary system activity. This study could be helpful to increase the clinical use of methylphenidate in the treatment of different disoders.


Assuntos
Buspirona/farmacocinética , Metilfenidato/farmacocinética , Ácido Vanilmandélico/urina , Animais , Buspirona/administração & dosagem , Masculino , Metilfenidato/administração & dosagem , Ratos Wistar
10.
Pak J Pharm Sci ; 31(5(Supplementary)): 2091-2094, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30393217

RESUMO

Among resistant nosocomial and community pathogens, MRSA has become the most serious pathogen, causing life threatening infections worldwide. In S.aureus, quick and exact recognition of methicillin (cefoxitin) resistance has become essential. The benchmark for MRSA identification among S.aureus is the detection of the mecA gene that causes the expression of protein (PBP2a) culpable for classic ß-lactam resistance. However, the utter reliance on amplification of mecA gene as a hallmark in confirmation of methicillin (cefoxitin) resistant S. aureus is the matter of distrust by some investigators. The current investigation designed to analyse the prevalence of mecA gene among phenotypically positive MRSA isolates using molecular method and to correlate its prevalence to conventional techniques. Furthermore, antimicrobial sensitivity of mecA positive staphylococci was determined by Kirby Baeuer method. For this purpose, 201 clinical staphylococcal specimens were recovered from various diagnostic laboratories in Karachi City, Pakistan. Phenotypic existence of methicillin resistance in S. aureus was observed to be 51.7%. In contrast, when organisms were subjected for amplification of mecA gene by PCR, mecA positive isolates were 36/104 (35%) MRSA isolates. Current work raise question towards the usefulness of molecular identification of mecA gene in confirmation of methicillin resistance without correlating with conventional methods. Therefore, it is essential to consider the other possible resistance mechanisms for ß-lactams that may interact with mecA gene in the development of methicillin resistance mechanism in Staphylococcus.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/epidemiologia , Testes Genéticos/métodos , Genótipo , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Proteínas de Ligação às Penicilinas/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Proteínas de Bactérias/genética , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/genética , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Paquistão/epidemiologia , Proteínas de Ligação às Penicilinas/genética , Prevalência , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/genética
11.
Pak J Pharm Sci ; 31(5): 1959-1965, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150195

RESUMO

Attenuation of methylphenidate-induced behavioral sensitization and cognitive tolerance by buspirone co-administration has been reported previously. Dopamine D2-receptors are considered to be important in methylphenidate-induced sensitization. This study was designed to monitor the responsiveness of D2 receptors following long-term methylphenidate, buspirone and their co-administration in rats by the challenge dose of haloperidol. Effects of haloperidol challenge dose (1 mg/kg i.p.) were monitored after 6 weeks (till the behavioral sensitization produced) from oral repeated (twice a day for 6 week) administration of methylphenidate (2mg/kg/day), buspirone (10mg/kg/day) and their co-administration. Motor activity was compared by using familiar environment of home cage and novel environment of open field and cognitive activity was compared by using water maze were monitored 30, 60, and 90 minutes post injection respectively. We found that haloperidol reduced motor activity in familiar as well as in novel environment and showed impaired cognitive performance in water maze. The effects were more pronounced in methylphenidate treated rats as compared to buspirone and methylphenidate co-administration treated rats. Increased response of haloperidol in methylphenidate treated rats can be explained in terms of super-sensitization of D2 receptors, which results in behavioral sensitization that is not observed in co-administration treated rats. Buspirone prevents D2 receptor's super-sensitization by increasing serotonergic inhibitory influence on dopamine neuron.


Assuntos
Buspirona/administração & dosagem , Cognição/efeitos dos fármacos , Haloperidol/administração & dosagem , Aprendizagem em Labirinto/efeitos dos fármacos , Metilfenidato/administração & dosagem , Atividade Motora/efeitos dos fármacos , Animais , Cognição/fisiologia , Antagonistas de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Combinação de Medicamentos , Aprendizagem em Labirinto/fisiologia , Atividade Motora/fisiologia , Ratos , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/metabolismo , Agonistas do Receptor de Serotonina/administração & dosagem
12.
Pak J Pharm Sci ; 31(3): 741-745, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29716850

RESUMO

Methylphenidate is commonly use for the treatment of attention deficit hyperactivity disorder (ADHD), but its long term use was found to produce hepatic necrosis in mice. Purpose of this study was to investigate that co-administration of buspirone (drug which attenuates methylphenidate induced sensitization) may attenuate methylphenidate-induced hepatotoxic effects and to determine the effect of challenge dose of haloperidol (D2 antagonist that blocks the effects of methylphenidate in case of intoxication) on SGPT and SGOT levels in methylphenidate treated rats. Estimation of SGPT and SGOT were performed using kit method. Prolong oral administration of methylphenidate at a dose of 2.0 mg/kg/day, buspirone at a dose of 10 mg/kg/day, their co-administration and challenge dose of haloperidol (1 mg/kg i.p.) in rats increased SGPT concentration and decreased SGOT concentration, effect is more pronounced in methylphenidate treated rats and potentiate with administration of haloperidol challenge dose. In conclusion our analysis showed that methylphenidate and challenge dose of haloperidol is associated with elevation of SGPT in rats, which is attenuate in co-administration of methylphenidate buspirone treated rats. To quantify the risk of methylphenidate-induced hepatic injury and role of buspirone to reduce the injury further pharmacoepidemiological investigations are required.


Assuntos
Ansiolíticos/uso terapêutico , Buspirona/uso terapêutico , Estimulantes do Sistema Nervoso Central/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Metilfenidato/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Masculino , Ratos
13.
Metab Brain Dis ; 33(3): 893-906, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29470766

RESUMO

Previous studies have demonstrated that repeated psychostimulant administration produces behavioural sensitization and cognitive tolerance. Brain dopaminergic system and the involvement of dopamine D2-receptors are considered to be important in psychostimulant-induced sensitization. Study designed to compared the motor activity by using familiar and novel enviroments and cognitive effects by water maze and passive avoidance test after long term administration of methylphenidate(at the dose 0.6 mg/kg/day, 2.5 mg/kg/day and 10 mg/kg/day) and modafinil (50 mg/kg/day, 64 mg/kg/day and 75 mg/kg/day) in rats. The effects of challenge dose of haloperidol (at the dose of 1 mg/kg i.p.) has monitored to visualize any subsensitization or supersensitization of D2 receptors. We found that motor activity and cognitive performance was increased in all doses and sensitization effect was more pronounced after 13 days of drug administration were greater at high than low and medium doses.Challenge dose of haloperidol attenuate motor activity in familiar and novel environment and impaired cognition in water maze and passive avoidance test in all treated rats. The effect of Haloperidol in high dose treated rats were however somewhat greater than low and medium dose treated rats following methylphenidate and modafinil administration. Increased response of haloperidol in methylphenidate treated rats can be explained in term of supersensitization of D2 receptors which is greater in high dose treated rats. The results show that the role of D2 receptors to develop side effects such as behavioural sensitization and cognitive tolerance by the long term administration of psychostimulants is of sufficient importance and helpful in understanding the mechanisms underlying the undesirable effects of psychostimulants.


Assuntos
Comportamento Animal/efeitos dos fármacos , Haloperidol/farmacologia , Metilfenidato/farmacologia , Modafinila/farmacologia , Nootrópicos/farmacologia , Animais , Antipsicóticos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos Sprague-Dawley
14.
Pak J Pharm Sci ; 30(2): 369-374, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28649058

RESUMO

Methylphenidate is effective in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults, but its long term use can cause potential adverse effect on growth rate and variable effects on appetite. Previous studies have shown that long term administration of psychostimulant drugs increases the effectiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors. Repeated administration of buspirone attenuates the effectiveness of somatodendritic 5-HT1A receptors. The present study was designed to test the hypothesis that co-administration of buspirone may attenuate methylphenidate-induced effects on growth rate and food intake. Growth rate was calculated weekly in terms of change in body weight as percentage of preceding week's body weight and food intake was calculated weekly by subtracting the amount of food left in the hopper from the amount of food placed in the hopper as % in preceding week mg/gm of body weight after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day decrease growth rate, but co-administration of buspirone at a dose of 10 mg/kg/day attenuates effect of methylphenidate on growth rate however food intake was significantly greater in all treated groups after 3 weeks of treatment. It is suggested that buspirone may oppose methylphenidate-induced growth inhibition by decreasing the sensitivity of somatodendritic 5-HT1A receptors. These findings may help to extend future therapeutics in ADHD.


Assuntos
Buspirona/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Metilfenidato/antagonistas & inibidores , Animais , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/antagonistas & inibidores , Interações Medicamentosas , Metilfenidato/efeitos adversos , Ratos
15.
Pak J Pharm Sci ; 29(2): 585-90, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27087081

RESUMO

Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD (attention deficit hyperactivity disorder), but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine (5-HT)-1A somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day enhanced motor activity in home cage i.e. activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13th day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10 mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD.


Assuntos
Comportamento Animal/efeitos dos fármacos , Buspirona/farmacologia , Estimulantes do Sistema Nervoso Central/toxicidade , Inibidores da Captação de Dopamina/toxicidade , Metilfenidato/toxicidade , Atividade Motora/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Administração Oral , Animais , Buspirona/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Esquema de Medicação , Metilfenidato/administração & dosagem , Ratos Wistar , Agonistas do Receptor de Serotonina/administração & dosagem , Fatores de Tempo
16.
Pak J Pharm Sci ; 28(5): 1601-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26408868

RESUMO

Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic 5HT-1A receptors effectiveness. Repeated buspirone administration attenuates 5-HT1A soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone co-administration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT 1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD.


Assuntos
Buspirona/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Metilfenidato/farmacologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Aprendizagem da Esquiva/efeitos dos fármacos , Tolerância a Medicamentos , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor 5-HT1A de Serotonina/efeitos dos fármacos
17.
Pak J Pharm Sci ; 28(1): 9-13, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25553710

RESUMO

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.


Assuntos
Regulação do Apetite/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Metilfenidato/administração & dosagem , Aumento de Peso/efeitos dos fármacos , Administração Oral , Animais , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Estimulantes do Sistema Nervoso Central/toxicidade , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Esquema de Medicação , Ingestão de Energia/efeitos dos fármacos , Metilfenidato/toxicidade , Ratos Wistar , Fatores de Tempo
18.
Pak J Pharm Sci ; 27(5 Spec no): 1509-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25176245

RESUMO

Chamomile is considered as one of the oldest and also documented as medicinal plant. It has shown to be an anti-inflammatory, astringent and antioxidant especially in floral part since ancient times. Recent studies reported that chamomile has potential to lower blood sugar levels in hyperglycemia. In the present study we have investigated the pharmacological effects of chamomile tea on fasting and post prandial glucose levels and HbA1C in blood of diabetic rats (alloxan induced) and the results were compared with glibenclamide as standard. Statistical analysis was performed using SPSS. It has been observed in our study that it has reduced progressively the fasting and post prandial blood sugar levels, significantly in alloxan induced diabetic rats particularly on day 30 and 60. It also reduced the level of HbA1C significantly at the end of the study and the effects were similar to that of the standard group. Chamomile tea administration has also controlled the reduction in weight in diabetic rats as compared to diabetic control and the results were not very much different from standard. Results from the present study indicate that chamomile tea have a glucose lowering effect in diabetic rats so its daily consumption can be potentially useful in hyperglycemia and it can be used as a substitute of conventional drug treatment. Further studies are necessary to elucidate the exact molecular mechanism involved in anti-diabetic action of chamomile.


Assuntos
Bebidas , Glicemia/efeitos dos fármacos , Camomila , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Flores , Glibureto/farmacologia , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/administração & dosagem , Injeções Intraperitoneais , Masculino , Fitoterapia , Extratos Vegetais/administração & dosagem , Plantas Medicinais , Ratos , Ratos Wistar , Fatores de Tempo
19.
Pak J Pharm Sci ; 24(3): 251-4, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21715256

RESUMO

Long term intake of coffee is known to produce anxiety and suppression of appetite. 5- hydroxytryptamine (5-HT) acting via 5-HT-2C receptors elicits anorexia and anxiety. The present study is design to monitor metachloro phenyl piperazine (m-CPP) at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion in rats taking a solution of caffeine (a component of coffee and tea) or theophylline (a component of tea) as a sole source of water. We found that hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline but not in caffeine treated animals suggesting that long term intake of theophylline may attenuate anorexiogenic and anxiogenic effects of 5-HT. A possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in people drinking coffee or tea discussed.


Assuntos
Cafeína/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Teofilina/farmacologia , Animais , Interações Medicamentosas , Piperazinas/antagonistas & inibidores , Ratos , Ratos Wistar
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