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P.6.056 Caffeine antagonizes the antinociceptive effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia
S380
P6, O~ker topics
temperature: 2 h be%re @re-drug group) or immediately after fentanyl citrate (0.1 mg/kg; iv) administration (post-drug group). Catalepsy was measured by using bar test (cut-off tim6 = 60 s) in 10 minutes intervals. In contrast to NAT, all rats exposed to HAT in pro-drug group assumed extended body posture. In all animals tested, catalepsy developed 1 min after injection of fentanyl citrate into the tail vein. In pro-drug group, cataleptic response to fentaw1 was significantly prolonged at NAT (up to 60 rain, n=8) in comparison to NAT (up to 30 min, n=9) @<0.05; MannWhitney TO test). Similarly to this, in post-drug group, cataleptic response to fentaw1 was prolonged at HAT (up to 60 rain, n=9) in comparison to NAT (up to 30 min, n=7) (p<0.05; Mann-Whitney U test). However, there was no difference between pro-drug and post-drug exposure of rats to NAT on the cataleptic response to fentanyl (p>0.05; Mann-Whitney U test). In conclusion, timing of exposure of rats to I-T_,_A_T(pro-drug vs. post-drug) does not affect the potentiation of the cataleptic effect of fentawh This finding suggests that HAT-induced thermoregulatory behaviour, observed during pro-drug exposure to RAT, is not implicated in the HAT-induced potentiation of the cataleptic effect of fentanyl in rats. More probably, it is result of the direct effect of HAT on the neuronal mechanisms underlying fentawl-induced catalepsy. The understanding of these mechanisrns will increase our basic understanding of brain function in hot environment.
right hind paw. Postdrug d was measured at 90, 150, 210, 270, 330 and 390 rain after drug administration. Control animals received the same volume of vehicle (i.p.) instead of test compounds. The ED50 is calculated using linear regression as the dose that was expected to result in 50% analgesic activity. Caffeine was injected i.p. at the contralateral side of peritoneum, immediately before the i.p. injection of ED50 of the carbamazepine or oxcarbazepine. Control animals received the same volume of saline (i.p.) instead of caffeine. The IDh0 is calculated using linear regression as the dose of caffeine which caused a 50% inhibition of antinociception. Caffeine (5-20 mg/kg; i.p.) significantly (p<0.05; Student's t-test) suppressed the antinociceptive effects of carbamazepine and oxcarbazepine in a dose-dependent manner. The corresponding ID50 4-S.E.M (confidence limits) values are 7.544-0.62 (2.62-21.7) mg/kg for caffeine+carbamazepine and 8.004-1.06 (1.4-43.8) mg/kg for caffeine+oxcarbazepine, respectively. This inhibitory effect of caffeine on the antinociceptive effect of carbamazepin6 and oxcarbazepin6, could be explained by pharmacokinetic and/or pharmacodynamic interaction. Further experiments need to be done in order to elucidate the mechanism of interaction between caffeine and carbamazepineloxcarbazepine. In conclusion, concomitant caffeine administration, as well as consumption of caffeine containing beverages, could possibly depress the analgesic effects of both anticonvulsive drugs.
References [1] Vuokovi% S.; Ivanovio, M.; Prostran, M.; Todorovi(',,Z.; Ristovi• Z.; Mioovi% 14 Beleslin, D., Higher environmental temperature potentiates cataleptic effect of fentanyl in rats. J Pharmaool Sot. 199S pp. 523-527. [2] Gordon, C.J., Thermal biol%G of the laboratory rat. Physiol & Behav. 1990 pp. 963-91.
References [1] Vaz, J., Kulkarni, C,, David, J., Joseph, T., 1998. Influence of caffeine on pharmaookinetio profile of sodium valproate and oarbamazepine in normal human volunteers. Indian J. Exp. Biol. 36, 112-114. [2] Mashimote, S., Ushijima, I., Saetsugi, M., Akimoto, Z, Watanabe, K., Yamada, M., 1998. Stress-depeadent antinooieeptive effects of oarbamazepine: a study in stressed and nonstressed rats. Pros Neuropsyohopharma¢ol. Biol. Psychiatry 22, 159-168.
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Caffeine antagonizes l~e antinociceptive effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia
•
Serum BDNF levels in conversion disorder: A comparative study with depression
R. Stepanovic-Petrovic 1, M. Tomic I , S. Vuckovic 2, N. Ugresic 1, M. Prostran 2., 1~, Boskovic s . 1Faculty of,Pl~armacy, University
A, Deveci 1, O, Aydemir 1, E,O, Taskin 1, F, Taneli 2, A, EsenDanaci j *, 1Celal Bayer U~ioersi~, P~yc~iatrN, Manisa, Turkey;
of Belgrade, Department of P~armacology, Belcgrade, Yugoslaoia; 2Faculty of Medicine, Unioersi~ of Belgrade, Depar~ent of Clinical Pharmacology, P~armacology and ToxicdogW, Belgrade, Yugoslavia; SMedicalMilita~ Academy, Department of Y~armacology and Toxicology, ~elgrade, Yugoslavia
2 Cola[ Bayar UniversitN, Biochemistry, Manisa, Turfey
It has been previously reported that concomitant administration of caffeine and carbamazepine resulted in reduction in plasma concentration and area under the concentration curve of cafoamazepine in healthy human volunteers (1). In animal study, caffeine (5 mg/kg, i.p.), inhibited antinociceptive effects of carbamazepine in stressed rats (2). The purpose of this study was to examine the influence of caffeine, as analgesic adjuvant and nonselective adenosine A1/A2 receptor antagonist, on the antinociceptNe effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia. Male Wistar rats (180-220 g) were used in the experiments. Each experimental group consisted of 6 to 8 rats. The antinociceptive activity was determined by modified "paw-pressure" test using the apparatus for evaluating the force exerted by rat hind paws in order to determine right/left differences. The difference (d) is calculated as: d = force (g) applied on healthy paw - force (g) applied on inflamed paw. Infiammatory hyperalgesia was induced 30 rain ares i.p. administration of drugs by iQecting 0.1 ml of 8 mg/ml solution of concanavalin A (Con A) intraplantarly (i.pl.) into the
Objective: Decreased BDNF levels may be important in the pathophysiology of depression. However, it has been thought that similar features in the neurobiology of conversion disorder and depression which are both related to stress may be associated. In this study, it is aimed to compare serum BDNF levels &patients with major depressive disorder and conversion disorder. Method: We measured serum BDNF levels in the following two groups: lwenty-four patients with major depressive disorder, fifteen patients with pure conversion disorder. Patients were evaluated using the Hamilton Rating Scale for Depression (HAM-D). Serum BDNF was assayed with an ELTSA Kit (Promega; Madison, WI, USA). In statistical analysis, T-Test were performed. Results: The mean age of the major depressive disorder group was 33.94-15.7; the mean age of the conversion disorder group was 30.44-11.9. Nine of the all patients were male (n:7, major depressive disorder group; n:2, conversion disorder group). We found that the two groups didn't differ significantly in terms of serum BDNF levels (mNor depressive disorder group, mean=21.2 ng/mL, SD=I 1.3; conversion disorder group, mean=24.3 ng/mL, SD=9). Conclusion: This study suggests that BDNF level may play a similar role in the pathophysiology of major depressive disorder and conversion disorder.
P6, O~ker topics
temperature: 2 h be%re @re-drug group) or immediately after fentanyl citrate (0.1 mg/kg; iv) administration (post-drug group). Catalepsy was measured by using bar test (cut-off tim6 = 60 s) in 10 minutes intervals. In contrast to NAT, all rats exposed to HAT in pro-drug group assumed extended body posture. In all animals tested, catalepsy developed 1 min after injection of fentanyl citrate into the tail vein. In pro-drug group, cataleptic response to fentaw1 was significantly prolonged at NAT (up to 60 rain, n=8) in comparison to NAT (up to 30 min, n=9) @<0.05; MannWhitney TO test). Similarly to this, in post-drug group, cataleptic response to fentaw1 was prolonged at HAT (up to 60 rain, n=9) in comparison to NAT (up to 30 min, n=7) (p<0.05; Mann-Whitney U test). However, there was no difference between pro-drug and post-drug exposure of rats to NAT on the cataleptic response to fentanyl (p>0.05; Mann-Whitney U test). In conclusion, timing of exposure of rats to I-T_,_A_T(pro-drug vs. post-drug) does not affect the potentiation of the cataleptic effect of fentawh This finding suggests that HAT-induced thermoregulatory behaviour, observed during pro-drug exposure to RAT, is not implicated in the HAT-induced potentiation of the cataleptic effect of fentanyl in rats. More probably, it is result of the direct effect of HAT on the neuronal mechanisms underlying fentawl-induced catalepsy. The understanding of these mechanisrns will increase our basic understanding of brain function in hot environment.
right hind paw. Postdrug d was measured at 90, 150, 210, 270, 330 and 390 rain after drug administration. Control animals received the same volume of vehicle (i.p.) instead of test compounds. The ED50 is calculated using linear regression as the dose that was expected to result in 50% analgesic activity. Caffeine was injected i.p. at the contralateral side of peritoneum, immediately before the i.p. injection of ED50 of the carbamazepine or oxcarbazepine. Control animals received the same volume of saline (i.p.) instead of caffeine. The IDh0 is calculated using linear regression as the dose of caffeine which caused a 50% inhibition of antinociception. Caffeine (5-20 mg/kg; i.p.) significantly (p<0.05; Student's t-test) suppressed the antinociceptive effects of carbamazepine and oxcarbazepine in a dose-dependent manner. The corresponding ID50 4-S.E.M (confidence limits) values are 7.544-0.62 (2.62-21.7) mg/kg for caffeine+carbamazepine and 8.004-1.06 (1.4-43.8) mg/kg for caffeine+oxcarbazepine, respectively. This inhibitory effect of caffeine on the antinociceptive effect of carbamazepin6 and oxcarbazepin6, could be explained by pharmacokinetic and/or pharmacodynamic interaction. Further experiments need to be done in order to elucidate the mechanism of interaction between caffeine and carbamazepineloxcarbazepine. In conclusion, concomitant caffeine administration, as well as consumption of caffeine containing beverages, could possibly depress the analgesic effects of both anticonvulsive drugs.
References [1] Vuokovi% S.; Ivanovio, M.; Prostran, M.; Todorovi(',,Z.; Ristovi• Z.; Mioovi% 14 Beleslin, D., Higher environmental temperature potentiates cataleptic effect of fentanyl in rats. J Pharmaool Sot. 199S pp. 523-527. [2] Gordon, C.J., Thermal biol%G of the laboratory rat. Physiol & Behav. 1990 pp. 963-91.
References [1] Vaz, J., Kulkarni, C,, David, J., Joseph, T., 1998. Influence of caffeine on pharmaookinetio profile of sodium valproate and oarbamazepine in normal human volunteers. Indian J. Exp. Biol. 36, 112-114. [2] Mashimote, S., Ushijima, I., Saetsugi, M., Akimoto, Z, Watanabe, K., Yamada, M., 1998. Stress-depeadent antinooieeptive effects of oarbamazepine: a study in stressed and nonstressed rats. Pros Neuropsyohopharma¢ol. Biol. Psychiatry 22, 159-168.
•
Caffeine antagonizes l~e antinociceptive effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia
•
Serum BDNF levels in conversion disorder: A comparative study with depression
R. Stepanovic-Petrovic 1, M. Tomic I , S. Vuckovic 2, N. Ugresic 1, M. Prostran 2., 1~, Boskovic s . 1Faculty of,Pl~armacy, University
A, Deveci 1, O, Aydemir 1, E,O, Taskin 1, F, Taneli 2, A, EsenDanaci j *, 1Celal Bayer U~ioersi~, P~yc~iatrN, Manisa, Turkey;
of Belgrade, Department of P~armacology, Belcgrade, Yugoslaoia; 2Faculty of Medicine, Unioersi~ of Belgrade, Depar~ent of Clinical Pharmacology, P~armacology and ToxicdogW, Belgrade, Yugoslavia; SMedicalMilita~ Academy, Department of Y~armacology and Toxicology, ~elgrade, Yugoslavia
2 Cola[ Bayar UniversitN, Biochemistry, Manisa, Turfey
It has been previously reported that concomitant administration of caffeine and carbamazepine resulted in reduction in plasma concentration and area under the concentration curve of cafoamazepine in healthy human volunteers (1). In animal study, caffeine (5 mg/kg, i.p.), inhibited antinociceptive effects of carbamazepine in stressed rats (2). The purpose of this study was to examine the influence of caffeine, as analgesic adjuvant and nonselective adenosine A1/A2 receptor antagonist, on the antinociceptNe effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia. Male Wistar rats (180-220 g) were used in the experiments. Each experimental group consisted of 6 to 8 rats. The antinociceptive activity was determined by modified "paw-pressure" test using the apparatus for evaluating the force exerted by rat hind paws in order to determine right/left differences. The difference (d) is calculated as: d = force (g) applied on healthy paw - force (g) applied on inflamed paw. Infiammatory hyperalgesia was induced 30 rain ares i.p. administration of drugs by iQecting 0.1 ml of 8 mg/ml solution of concanavalin A (Con A) intraplantarly (i.pl.) into the
Objective: Decreased BDNF levels may be important in the pathophysiology of depression. However, it has been thought that similar features in the neurobiology of conversion disorder and depression which are both related to stress may be associated. In this study, it is aimed to compare serum BDNF levels &patients with major depressive disorder and conversion disorder. Method: We measured serum BDNF levels in the following two groups: lwenty-four patients with major depressive disorder, fifteen patients with pure conversion disorder. Patients were evaluated using the Hamilton Rating Scale for Depression (HAM-D). Serum BDNF was assayed with an ELTSA Kit (Promega; Madison, WI, USA). In statistical analysis, T-Test were performed. Results: The mean age of the major depressive disorder group was 33.94-15.7; the mean age of the conversion disorder group was 30.44-11.9. Nine of the all patients were male (n:7, major depressive disorder group; n:2, conversion disorder group). We found that the two groups didn't differ significantly in terms of serum BDNF levels (mNor depressive disorder group, mean=21.2 ng/mL, SD=I 1.3; conversion disorder group, mean=24.3 ng/mL, SD=9). Conclusion: This study suggests that BDNF level may play a similar role in the pathophysiology of major depressive disorder and conversion disorder.