Background and Objective: Gabapentin is a commonly prescribed antiepileptic agent for seizures, which is also used for pain and addiction management. Due to growing evidence of its abuse liability, there has been an incentive to synthesise potentially useful gabapentin derivatives devoid of adverse effects. A gabapentin adduct with a fluoxetine moiety, GBP1F, was assessed for any sedative, cognitive, anxiolytic, or antidepressant-like actions in murine behavioral models. Materials and Methods: Selected groups of mice were used for each behavioral paradigm, and the effect of GBP1F (5, 10, and 15 mg/kg) was assessed using spontaneous locomotor activity, the tail suspension test, elevated plus maze test, and the Y maze test models. Immediately following behavioral experiments, postmortem striatal and hippocampal tissues were evaluated for the effect of GBP1F on concentrations of dopamine, DOPAC, HVA, serotonin, 5-HIAA, vitamin C, and noradrenaline using high performance liquid chromatography with electrochemical detection. Results: GBP1F induced a mild suppression of locomotor activity, ameliorated anxiety and depression-like behavior, did not alter cognitive behavior, and raised serotonin and 5-HIAA concentrations in the hippocampus and striatum. GBP1F also positively enhanced dopamine and vitamin C tissue levels in the striatum. Thus, GBP1F represents a compound with anxiolytic- and antidepressant-like effects though further studies are warranted at the molecular level to focus on the precise mechanism(s) of action.
Anti-Anxiety Agents , Fluoxetine , Mice , Animals , Fluoxetine/pharmacology , Gabapentin/pharmacology , Dopamine/pharmacology , Depression/drug therapy , Serotonin , Anti-Anxiety Agents/pharmacology , Hydroxyindoleacetic Acid/pharmacology , Disease Models, Animal , Antidepressive Agents/pharmacology , Anxiety , Cognition , Ascorbic Acid/pharmacology , Behavior, Animal
INTRODUCTION: Behavioral sensitization is a phenomenon that develops from intermittent exposure to nicotine and other psychostimulants, which often leads to heightened locomotor activity and then relapse. Sulfonamides that act as carbonic anhydrase inhibitors have a documented role in enhancing dopaminergic tone and normalizing neuroplasticity by stabilizing glutamate release. OBJECTIVE: The aim of the current study was to explore synthetic sulfonamides derivative 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS) (with documented carbonic anhydrase inhibitory activity) on acquisition and expression of nicotine-induced behavioral sensitization. METHODS: In the acquisition phase, selected 5 groups of mice were exposed to saline or nicotine 0.5mg/kg intraperitoneal (i.p) for 7 consecutive days. Selected 3 groups were administered with 4-FBS 20, 40, and 60 mg/kg p.o. along with nicotine. After 3 days of the drug-free period, ie, day 11, a challenge dose of nicotine was injected to all groups except saline and locomotor activity was recorded for 30 minutes. In the expression phase, mice were exposed to saline and nicotine only 0.5 mg/kg i.p for 7 consecutive days. After 3 days of the drug-free period, ie, day 11, 4-FBS at 20, 40, and 60 mg/kg were administered to the selected groups, one hour after drug a nicotine challenge dose was administered, and locomotion was recorded. At the end of behavioral experiments, all animals were decapitated and the striatum was excised and screened for changes in adenosine levels, using HPLC-UV. RESULTS: Taken together, our findings showed that 4-FBS in all 3 doses, in both sets of experiments significantly attenuated nicotine-induced behavioral sensitization in mice. Additionally, 4-FBS at 60mg/kg significantly lowered the adenosine level in the striatum. CONCLUSION: The behavioral and adenosine modulation is promising, and more receptors level studies are warranted to explore the exact mechanism of action of 4-FBS.
Adenosine/antagonists & inhibitors , Behavior, Animal/drug effects , Benzene Derivatives/pharmacology , Nicotine/antagonists & inhibitors , Nicotinic Antagonists/pharmacology , Sulfonamides/pharmacology , Adenosine/metabolism , Administration, Oral , Animals , Benzene Derivatives/administration & dosage , Benzene Derivatives/chemical synthesis , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Male , Mice , Mice, Inbred BALB C , Nicotine/administration & dosage , Nicotinic Antagonists/administration & dosage , Nicotinic Antagonists/chemical synthesis , Sulfonamides/administration & dosage , Sulfonamides/chemical synthesis
The main objective of this study was to assess the practice at retail pharmacies in Pakistan and to compare the same in rural and urban areas. The maintenance of pharmacy and drug inspectors' visit was also assessed. This cross sectional study was conducted in Abbottabad, Pakistan during October-November, 2012. A sample of 215 drug sellers or drug stores was selected by employing convenient sampling method. With a response rate of 91.6%, 197 drug sellers participated in this study. All the drug sellers were male. Overall, 35% (n = 197) of the drug sellers did not have any professional qualification. A majority of the drug sellers were involved in various malpractices like selling of medicines without prescription (80.7%), prescribing practice (60.9%), prescription intervention (62.4%) and selling of controlled substances (66%) without a license for selling it. These malpractices were significantly higher in rural area than that in urban area.
Legislation, Drug/trends , Legislation, Pharmacy/trends , Pharmacies/statistics & numerical data , Pharmacies/standards , Community Pharmacy Services , Controlled Substances , Cross-Sectional Studies , Drug Prescriptions , Humans , Pakistan , Rural Population , Urban Population
Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol-induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose-dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization.
Benzoquinones , Ethanol/administration & dosage , Alcohol Drinking/drug therapy , Alcohol Drinking/psychology , Animals , Male , Mice , Plant Oils
