Isik Tuglular

The antinociceptive effect of tramadol on a model of neuropathic pain in rats.

The antinociceptive activity of tramadol was investigated on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. Despite the analgesic activity of tramadol was clearly established in motor and sensory responses of the nociceptive system in rats, the effect of this atypical opioid on experimental neuropathic pain models is not investigated. The intraperitoneally injected tramadol (2.5, 5 and 10 mg/kg) produced a potent and dose-dependent antinociceptive effect on both lesioned and non-lesioned hind paws. However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. This effect was partially antagonized by intraperitoneally administered naloxone (0.1 mg/kg) suggesting an additional non-opioid mechanism. Our results suggest that tramadol may be useful for the alleviation of some symptoms in peripheral neuropathic conditions

Hypericum triquetrifolium Turra. extract exhibits antinociceptive activity in the mouse.

The aim of the present study was to investigate the antinociceptive activity of Hypericum triquetrifolium Turra. extract. The lyophilized extract was administered to male Swiss mice. Formalin paw test and tail flick tests were used for the evaluation of the antinociceptive activity. Plant extract (10, 25, 50 and 60 mg kg(-1), i.p.) (n = 16-24 for each group) or vehicle (n = 27) was administered 30 min before the subplantar formalin injection. In the tail flick test, mice were examined for latency to withdraw their tails from a noxious thermal stimulus using a tail flick meter (n = 8 for each group). The effects of the extract on sensorimotor performance was also assessed (n = 16-24 for each group). The extract caused a significant dose-related inhibition of the first phase (50, 60 mg kg(-1), i.p.) and second phase (10, 25, 50 and 60 mg kg(-1), i.p.) of formalin induced hindpaw licking. Additionally, the extract administration (50, 60 mg kg(-1), i.p.) increased the tail flick latencies. No significant change was observed in any of the treatment groups in the sensorimotor performance test. The observed antinociceptive activity of the extract may be due to its noradrenaline and serotonin reuptake blocking activity. Moreover, the probable antiinflammatory activity of the extract may play a role in the dose-related inhibition of the second phase of formalin paw test.

Analgesic effect of tianeptine in mice.

The effects of tianeptine, a novel and unusual tricyclic antidepressant drug, on tail-flick and hot-plate tests, which are two thermal analgesia evaluating methods, have been investigated in mice. Tianeptine (5 and 10 mg/kg), para-chlorophenylalanine (pCPA) (100 mg/kg) and a combination of pCPA and tianeptine (10 mg/kg) or saline were injected to mice intraperitoneally. pCPA (100 mg/kg) was injected 24 h before tianeptine or saline treatment when it was combined with tinaeptine (10 mg/kg) or tested alone. The tail-flick latencies and hot-plate reaction times of the mice were measured between 15th and 180th minutes following injections. Tianeptine (10 mg/kg) exhibited a significant antinociceptive activity that could be measured by both tests as compared to groups which were treated with saline or pCPA alone between 15th and 180th min of the observation period. The lower dose of tianeptine (5 mg/kg) or pCPA (100 mg/kg) did not produce any significant changes on tail-flick latency or hot-plate reaction time of the mice. However, pretreatment with pCPA completely blocked the antinociceptive effect induced by tianeptine (10 mg/kg) in both tests used in the present study. Furthermore, tianeptine (10 mg/kg) did not cause any significant impairment effects on rotarod performance of the mice. Our results suggested that tianeptine has a prominent thermal antinociceptive activity in mice and that increased serotonergic activity may be responsible for the analgesic effect of tianeptine.

Renal side-effects of long-term lithium treatment.

The beta 2-Mg (beta 2-microglobulin) and GAG (glycosaminogyclan) excretions in 107 patients with bipolar disorder who had been on lithium treatment for 1-15 years were compared with 29 matched psychiatric control patients. 24-h urine volume, urine beta 2-Mg, GAG values were significantly higher, and maximal urinary osmolality was significantly lower in patients on lithium than in controls. No relationship was found between creatinine clearances and duration of illness, duration of lithium treatment and daily lithium dosages. Duration of lithium treatment was not related to the concentrating capacity. The beta 2-Mg excretion rates were significantly higher in patients with manifest polyuria and with severe concentration defect.

The orthodox-paradoxical sleep cycle in the rat

Under the postulated existence of a mechanism regulating the NREM sleep-REM sleep sequence and a reset of this mechanism by long awakenings, the variability of sleep cycle in the rat was studied. Awakenings of various durations were included in the definition of sleep cycle boundaries. Results show that an intervening awakening of 1 min is close to the limit under which the same cycle seems to be resumed after the awakening and above which the previous cycle is abortive and a new cycle will start after the next sleep onset.

Long-term efficacy of sertraline in the prevention of alcoholic relapses in alcohol-dependent patients: A single-center, double-blind, randomized, placebo-controlled, parallel-group study

Background: Alcoholism may be related to dysfunction of the serotonergic system in some patients. Therapy with a selective serotonin reuptake inhibitor (SSRI) may help to reduce alcohol consumption in these patients. Objective: The aim of this study was to examine the long-term efficacy of the SSRI sertraline in preventing alcoholic relapse and in increasing the number of abstinent days after alcohol withdrawal in alcohol-dependent patients. Methods: Male patients who met the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) diagnostic criteria for alcohol dependence with no concurrent disorders on Axis I participated in this single-center, double-blind, randomized, placebo-controlled, parallel-group study. All of the patients had been withdrawn from alcohol for 7 to 21 days when included in the study during their inpatient treatment and were followed up for 6 months with monthly assessments. Patients were given either two 50-mg capsules of sertraline hydrochloride daily (100 mg/d) or 2 placebo capsules daily. Results: A total of 59 patients (mean [SD] age, 43.8 [8.5] years) were enrolled (30 in the sertraline group and 29 in the placebo group). The 2 groups differed significantly in terms of the mean (SD) number of abstinent days (sertraline, 125.5 [60.6] days; placebo, 91.9 [66.4] days; P = 0.047). Although the percentage of relapse was lower in the sertraline group in all monthly assessments, the difference in percentage of relapse between the 2 groups reached statistical significance only at month 4 (P = 0.027). Conclusions: Sertraline seems to increase the number of abstinent days and thus has a preventive effect on alcoholic relapse. However, this finding needs to be supported by further controlled studies.

Pharmacokinetics of carbamazepine Part I: a new bioequivalency parameter based on a relative bioavailability trial

SummaryThe relative bioavailability of three carbamazepine generics available in Turkey, were investigated in 5 healthy male volunteers. When issuing a license to any drug, FDA stipulates at most a difference of 20% from the reference drug only in peak concentration and AUC (area under the curve). This condition may cause some problems, as two generics of the same drug can yield the same total amount (AUC) and can be accepted as bioequivalent despite different curves of the two drugs. In this study, to compare drugs from the point of view of bioequivalency, we suggest a new calculation method that takes into account ka (absorption rate constant), ke (elimination rate constant), tmax (time to peak), MRT (mean residence time) and AUC. Should this formula be used in comparison of bioequivalency, all the parameters related to the kinetics of drugs will have been taken into account. The suggested parameter is:

An attempt to predict daily erythrocyte lithium fluctuations

\begin{gathered} A = \frac{{k_e \times (MRT - t_{\max } )}}{{k_a \times t_{\max } }} \times AUC_{0 \to \infty } \hfill \\ and \hfill \\ Bioequivalency = \frac{{A_{Drug1} }}{{A_{Drug2} }} \hfill \\ \end{gathered}