scholarly journals Influence of ketotifen and conventional antiepileptic drugs on the exploratory and spontaneous locomotor activity in mice

2020 ◽  
Vol 33 (4) ◽  
pp. 206-210
Author(s):  
Izabela Zakrocka ◽  
Katarzyna Swiader ◽  
Mariusz Swiader
Keyword(s):  
Locomotor Activity ◽  
Spontaneous Activity ◽  
Antiepileptic Drugs ◽  
Test Performance ◽  
Total Activity ◽  
Inappropriate Drug ◽  
Drug Selection ◽  
Vertical Activity ◽  
Second Period

Abstract Drug interactions are major problems in polytherapy, especially in epilepsy, and inappropriate drug selection may result in increased frequency of seizures. In this study, the influence of histamine type 1 (H1) receptor antagonist ketotifen and four chosen antiepileptic drugs (AEDs) on mice activity was examined. We evaluated three parameters of locomotor activity in mice: horizontal total activity with total distance and vertical activity, as well as animal spontaneous activity. Experiments were divided into two 15-minutes studies. During the first 15 minutes, we examined exploratory activity in mice; in the second period, spontaneous activity was tested. In the experiment, Ketotifen or vehicle were administered once or for 7 days daily, whereas AEDs were given only once before test performance. Our results show that ketotifen given alone once or for 7 days significantly increased exploratory locomotor activity in mice without affecting their spontaneous activity. However, in combination with AEDs, ketotifen given once or for 7 days differently affected spontaneous and locomotor activity in mice. Our study indicates that the combination of ketotifen with AEDs needs special attention in pharmacotherapy of epilepsy.

Effect of Nonsedative Doses of Propofol on an Innate Anxiogenic Situation in Rats 

1999 ◽  
Vol 90 (1) ◽  
pp. 191-196 ◽  
Author(s):  
Laure Pain ◽  
Philippe Oberling ◽  
Anne Launoy ◽  
Georges Di Scala
Keyword(s):  
Animal Model ◽  
Locomotor Activity ◽  
Spontaneous Activity ◽  
Total Activity ◽  
Sedative Effect ◽  
Exploratory Activity ◽  
Spontaneous Locomotor Activity ◽  
Initial Exposure ◽  
Open Platform ◽  
Standard Animal

Background The effect of propofol on anxiety has not been well studied. In humans, such investigations are confused by the fact that sedation often coexists with anxiolysis. Therefore, the authors evaluated the effects of minimal sedation with propofol in rats placed in an innate anxiogenic situation, the elevated plus-shaped maze. Methods In experiment 1, spontaneous locomotor activity was determined in rats as a measure of sedative effect induced by propofol (0-9 mg/kg administered intraperitoneally). In experiment 2, groups of rats received propofol (0-9 mg/kg) or diazepam (0-2 mg/kg) and then were placed on a plus-shaped maze elevated above the ground that was composed of two opposite closed arms and two opposite open arms. On an initial exposure to the maze, undrugged rats avoid the open arms, with the number of entries into and time spent within the open arms constituting approximately 20% of their total activity. This reflects normal anxiety in a rodent for any elevated open platform. Results In experiment 1, 0-9 mg/kg propofol did not alter spontaneous activity in rats. In experiment 2, propofol and diazepam significantly increased the number of entries into and the time spent within the open arms. Propofol at a dose of 9 mg/kg significantly increased the rats' level of exploration of the open arms to about 50% of all exploratory activity, and a similar observation was made with 2 mg/kg diazepam. Conclusions In a standard animal model, propofol has anxiolytic properties at doses that do not produce sedation.

scholarly journals Effect of famotidine in combination with antiepileptic drugs on locomotor activity in mice

2019 ◽  
Vol 32 (1) ◽  
pp. 10-13
Author(s):  
Mariusz J. Swiader ◽  
Katarzyna Swiader ◽  
Izabela Zakrocka ◽  
Darin Munir
Keyword(s):  
Locomotor Activity ◽  
Antiepileptic Drugs ◽  
The Other ◽  
Ulcer Disease ◽  
Antiepileptic Agents ◽  
Total Distance ◽  
Vertical Activity ◽  
Horizontal Activity ◽  
Patients With Epilepsy

Abstract Histamine type 2 receptor antagonists are one of the most commonly used agents to treat peptic ulcer disease. Since patients with epilepsy may have many comorbidities, the aim of this study was to investigate the influence of one of the strongest second generation histamine type 2 receptor antagonist, famotidine, on the exploratory and spontaneous activity in mice after 1 or 7 days treatment. Additionally, the interaction between famotidine and antiepileptics: carbamazepine, phenytoin, phenobarbital or valproate and their effect on animals activity was also evaluated. Locomotor activity was monitored electronically using a Digiscan analyzer in relation to ambulatory and rearing activities, as well as total distance travelled by animals during 15 minute periods. Results of our study indicate that famotidine administered alone did not modulate three variables of exploratory motor activity (horizontal activity, total distance and vertical activity) in mice. On the other hand, famotidine co-administered with valproate (1 day) or phenobarbital (1 day or 7 days) worsened vertical activity in mice in exploratory time. Similarly, impairment in horizontal activity in mice was observed when famotidine was given with phenobarbital (1 or 7 days). An increase in total distance in mice after famotidine alone or in combination with tested antiepileptic drugs was also shown. Moreover, famotidine alone or together with antiepileptic agents significantly impaired spontaneous locomotor activity in mice. The presented results show that famotidine administration to patients with epilepsy should be considered as potentially hazardous.

Neuropharmacological Screening of Chiral and Non-chiral Phthalimide- Containing Compounds in Mice: in vivo and in silico Experiments

2019 ◽  
Vol 15 (1) ◽  
pp. 102-118 ◽  
Author(s):  
Carolina Campos-Rodríguez ◽  
José G. Trujillo-Ferrara ◽  
Ameyali Alvarez-Guerra ◽  
Irán M. Cumbres Vargas ◽  
Roberto I. Cuevas-Hernández ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
In Silico ◽  
Biological Properties ◽  
Chiral Molecules ◽  
Chiral Compounds ◽  
Plus Maze ◽  
In Silico Studies ◽  
The Central Nervous System

Background: Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. Objective: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. Method: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). Results: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. Conclusion: The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia

2009 ◽  
Vol 29 (S 01) ◽  
pp. S98-S102 ◽  
Author(s):  
B. Huhn ◽  
A. Hofmann ◽  
K. Hofmann ◽  
H. Sirb ◽  
V. Aumann ◽  
...  
Keyword(s):  
Partial Response ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Vascular Endothelium ◽  
Test Performance ◽  
Coagulation Factor ◽  
Syndrome Type ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe influence of desmopressin on hemostasis is mediated by the release of von Willebrand factor and of coagulation factor VIII from vascular endothelium. The necessity of testing desmopressin effectiveness on hemostasis is a matter of controversy and the performance of the test is not yet standardized. For this reason the desmopressin tests in 114 children with von Willebrand syndrome (type 1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric haemostaseologic centers were retrospectively analyzed. The effectiveness of desmopressin was assessed using defined response criteria. As expected, the test performance showed a wide variation among the centers. In 99 children desmopressin was given intravenously as a short infusion at a dosage ranging from 0.25 to 0.41 μg/kg and in 15 intranasally at an absolute dose of 40 to 300 μg. The points of time for blood taking after desmopressin application ranged from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the partial response in 15 indicate the necessity of testing desmopressin effectiveness before the first therapeutic use. The application of desmopressin was well tolerated by the patients.

scholarly journals Protein phosphatase composition in the smooth muscle of guinea-pig ileum studied with okadaic acid and inhibitor 2

1989 ◽  
Vol 262 (2) ◽  
pp. 617-623 ◽  
Author(s):  
A Takai ◽  
M Troschka ◽  
G Mieskes ◽  
A V Somlyo
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Okadaic Acid ◽  
Total Activity ◽  
Guinea Pig Ileum ◽  
Control Activity ◽  
Triton X ◽  
Type 1 Phosphatase ◽  
Intracellular Structure

Using okadaic acid, a potent inhibitor of type 2A and type 1 protein phosphatases, and inhibitor 2, an intrinsic inhibitory factor of type 1 phosphatase, we characterized the phosphorylated myosin light-chain (PMLC) phosphatase activity in the smooth-muscle extracts of guinea-pig ileum. In the intact fibres the control activity was 254 +/- 13 nmol of Pi/min per g wet wt. (n = 15) against 32P-labelled PMLC (4 microM) from chicken gizzard. The following phosphatase fractions were identified: an inhibitor-2-sensitive (type 1) fraction (fractional activity = 35%), a Mg2+-dependent and okadaic acid-insensitive (type 2C) fraction (17%), and two type 2A-like fractions that had different susceptibility to okadaic acid. The type 2A-like fraction with lower affinity to okadaic acid accounted for 30% of the control activity. After the cell membrane was permeabilized by Triton X-100, more than 60% of this fraction remained and accounted for about 90% of the total activity, whereas the other fractions were nearly abolished. The type 2A-like fraction may be bound to some intracellular structure such as contractile proteins.

scholarly journals Activation of neurotensin receptor type 1 attenuates locomotor activity

2014 ◽  
Vol 85 ◽  
pp. 482-492 ◽  
Author(s):  
Chelsea A. Vadnie ◽  
David J. Hinton ◽  
Sun Choi ◽  
YuBin Choi ◽  
Christina L. Ruby ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Receptor Type ◽  
Neurotensin Receptor

scholarly journals Diagnostic Performance of Plasma Gastrin Concentration for the Diagnosis of Type 1 Abomasal Ulcer in Water Buffalo: A Preliminary Case Control Study

2021 ◽  
Author(s):  
Syed Ashaq Hussain ◽  
S K Uppal ◽  
N K Sood
Keyword(s):  
Test Performance ◽  
Predictive Value ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Plasma Gastrin ◽  
Roc Curve Analysis ◽  
Optimal Value ◽  
Sensitivity Specificity ◽  
Control Study

Abstract The type 1 abomasal ulcer (AU1) does not have specific clinical signs, and there is a need to identify some early biochemical markers for diagnosis of AU1 in cattle and buffaloes. Plasma gastrin is reported to reflect the gastric mucosa damage but its utility for diagnosis of AU1 in buffaloes has not been evaluated. The objective of this study was to study the test performance of plasma gastrin to distinguish healthy buffaloes and buffaloes with AU1. Twenty-three buffaloes with AU1 and six buffaloes without abomasal ulcer were used. Blood samples were collected from the buffaloes, slaughtered in a buffalo specific slaughter house, for estimation of plasma gastrin. After slaughter abomasa were examined for presence of AU1 and were confirmed by histology. The mean plasma gastrin concentration of ulcer positive buffaloes was significantly (p<0.05) higher than the ulcer negative buffaloes. The ROC curve analysis suggested optimal value of plasma gastrin for diagnosis of AU1 was 106.2 pg/ml. Since the abomasal ulcer negative animals were established to be ulcer negative on histopathological examination we consider the values of gastrin valid for detection of abomasal ulceration in buffaloes. The sensitivity, specificity, positive predictive value and negative predictive value of plasma gastrin to diagnose AU1 in buffalo were 78.3, 100, 100 and 69.9, respectively.

Central nervous system effects of caffeine and adenosine on fatigue

2003 ◽  
Vol 284 (2) ◽  
pp. R399-R404 ◽  
Author(s):  
J. Mark Davis ◽  
Zuowei Zhao ◽  
Howard S. Stock ◽  
Kristen A. Mehl ◽  
James Buggy ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Locomotor Activity ◽  
Spontaneous Activity ◽  
Adenosine Receptors ◽  
Receptor Agonist ◽  
Treadmill Running ◽  
Male Rats ◽  
Caffeine Ingestion ◽  
Run Time

Caffeine ingestion can delay fatigue during exercise, but the mechanisms remain elusive. This study was designed to test the hypothesis that blockade of central nervous system (CNS) adenosine receptors may explain the beneficial effect of caffeine on fatigue. Initial experiments were done to confirm an effect of CNS caffeine and/or the adenosine A1/A2 receptor agonist 5′- N-ethylcarboxamidoadenosine (NECA) on spontaneous locomotor activity. Thirty minutes before measurement of spontaneous activity or treadmill running, male rats received caffeine, NECA, caffeine plus NECA, or vehicle during four sessions separated by ∼1 wk. CNS caffeine and NECA (intracerebroventricular) were associated with increased and decreased spontaneous activity, respectively, but caffeine plus NECA did not block the reduction induced by NECA. CNS caffeine also increased run time to fatigue by 60% and NECA reduced it by 68% vs. vehicle. However, unlike the effects on spontaneous activity, pretreatment with caffeine was effective in blocking the decrease in run time by NECA. No differences were found after peripheral (intraperitoneal) drug administration. Results suggest that caffeine can delay fatigue through CNS mechanisms, at least in part by blocking adenosine receptors.

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