Feb 2017 DOI 10.14302/issn.2476-1710.jdt-16-1346
D. Deiko RomanCorresponding author
Post-graduate student of the department of pharmacology of National University of Pharmacy
Theaim of study is to evaluate antidepressant-like activity of the new peptidergic neuroprotectoracetyl-(D-Lys)-Lys-Arg-Arg-amide, homologous of ACTH15-18 primary amino acids sequence, that demonstrates nootropic and neuroprotective properties. Using Porsolt swimming test (PST) efficacy of tetrapeptide neuroprotector KK-1 at a single dose of 0.02 mg/kg was investigated on 16 white random bred male rats (body mass equaled 180-220 grams). Imipramine (15 mg/kg i.p.) was used as a reference drug. Then depression was induced in these rats by reserpine (4 mg/kg, i.p.). The KK-1 (intranasally, i.n.) and imipramine were administered once a day during 3 days until the reserpine-induced depression was reproduced. The indices of rats behavior under the conditions of open-field test (OFT) and PST were evaluated. The influence of both drugs on specific reserpine-induced depressions symptoms (hypothermia and blepharoptosis) was also registered. The results were processed statistically. The tetrapeptide neuroprotector KK-1 reduced immobilization time of rats at PST (statistically significant differences compared with control group), exceeding efficacy of reference drug imipramine. Normalizing of locomotor and exploratory activity in the OFT, decreasing indices of rats helplessness behavior in PST by tetrapeptide neuroprotector KK-1 demonstrates its antagonism with depressive action of reserpine. The tetrapeptide KK-1 showed antidepressant-like action both in intact rats and in rats with the model of reserpine-induced depression. It reduced specific symptoms of depression – hypothermia and blepharoptosis, exceeding the activity of reference drug imipramine.
Nov 2013 DOI 10.14302/issn.2328-0182.japst-13-185
WS WaringCorresponding author
Acute Medical Unit, York Hospital, York, UK
Background: Antidepressant agents are commonly implicated in drug overdose, and the toxicological profile varies between agents. Clinical data concerning overdoses are not systematically sought or evaluated in pharmacovigilance. The present study sought to examine the feasibility of collecting Emergency Department data concerning antidepressant overdose. Methods : Presentations to York Hospital due to intentional antidepressant overdose were studied between 2010 and 2011. Data collected were the type of antidepressant, dose, co-ingested drugs, duration of hospital stay, and need for critical care. Community National Health Service prescription data were evaluated across York and North Yorkshire region. Results : There were 250 overdose episodes. These involved a selective serotonin reuptake inhibitor (SSRI) in 183 (73.2%), and a tricyclic in 45 (18.0%), equivalent to 24 episodes per 100,000 prescription items (95% CI 21-28 per 100,000) and 11 per 100,000 (8-15 per 100,000) respectively (P<0.0001). Citalopram was the most commonly prescribed, and associated with 22 overdose episodes per 100,000 (17-27 per 100,000). Fluoxetine was associated with 32 overdose episodes per 100,000 (24-41 per 100,000) (P=0.032 versus citalopram), whereas the lower rates were observed for amitriptyline (13, 9-17 per 100,000) (P=0.004) and dosulepin (2, 0-10 per 100,000) (P=0.001). Conclusions : A higher than expected number of overdose episodes involved an SSRI based on National Health Service primary care prescribing, and fewer episodes involved a tricyclic antidepressant. Clinical outcomes differed between agents, indicating the feasibility of using Emergency Department data to detect different patterns of toxicity between antidepressants. Further work is required to examine whether systematic collection of clinical toxicology data might enhance existing pharmacovigilance systems.