게시판
| 21KS-041 |
Synergistic Antiallodynic effect of intraperitoneal Dexmedetomidne and Paroxetine in mice with a nerve ligation injury
울산대학교 의과대학 마취통증의학교실
Background: Dexmedetomidine is an α2 presynaptic inhibitor and decreases noradrenergic activity.
Dexmedetomidine is used in clinical practice as a sedative, analgesic, and sympatholytic. Rapid IV administration or bolus has been associated with hypertension due to peripheral α2-receptor stimulation. Sometimes bradycardia can be occurred.
Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, etc. Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, and sexual dysfunction. It is believed to work by blocking the re-uptake of the chemical serotonin by neurons in the brain.
Sedation can be caused by Dexmedetomidine and drowsiness could be caused by Paroxetine. Therefore, we could simply suggest that the antiallodynic effect would be increased with co-administration of Dexmedetomidine and Paroxetine.
Both drugs have no common pathway of action mechanism. So we could suggest just additive effect of both drugs. On the other hand, we could suggest synergistic effect of both drugs caused by sedation and drowsiness.
In the present study, it was designed to investigate the antiallodynic effect of Dexmedetomidine and its possible interaction with Paroxetine in the mice model of nerve ligation injury.
Methods: The experiments were conducted in male ICR mice (25-35 g).
To create the neuropathic mouse model, the left L5 and L6 spinal nerves were gently isolated and ligated tightly with 6-0 black silk.
The tactile allodynia was measured with von Frey Filaments using the up-down method. To determine whether the drug interaction between Dexmedetomidine and Paroxetine is additive or synergistic, an equal dose ratio isobolographic analysis was performed. ( Dexmedetomidine 1, 3, 8, 25 μg/kg, Paroxetine 0.6, 2, 6, 20 mg/kg, intraperitoneal)
Results: Intraperitoneal Dexmedetomidine and Paroxetine alone produced a dose-dependent reduction of tactile allodynia.
A Dexmedetomidine-Paroxetine combination produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction after the coadministration of Dexmedetomidine and Paroxetine.
Conclusions: Intraperitoneally administered Dexmedetomidine or Paroxetine produced dose-dependent antiallodynia.
Antiallodynic effect of intraperitoneal Dexmedetomidine, when combined with intraperitoneal Paroxetine, is synergistic in a mice model of nerve ligation injury.
We could suggest the synergistic interaction may be caused by sedation and drowsiness. Therefore, we have to take care when coadministration of both drugs.
Dexmedetomidine is used in clinical practice as a sedative, analgesic, and sympatholytic. Rapid IV administration or bolus has been associated with hypertension due to peripheral α2-receptor stimulation. Sometimes bradycardia can be occurred.
Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, etc. Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, and sexual dysfunction. It is believed to work by blocking the re-uptake of the chemical serotonin by neurons in the brain.
Sedation can be caused by Dexmedetomidine and drowsiness could be caused by Paroxetine. Therefore, we could simply suggest that the antiallodynic effect would be increased with co-administration of Dexmedetomidine and Paroxetine.
Both drugs have no common pathway of action mechanism. So we could suggest just additive effect of both drugs. On the other hand, we could suggest synergistic effect of both drugs caused by sedation and drowsiness.
In the present study, it was designed to investigate the antiallodynic effect of Dexmedetomidine and its possible interaction with Paroxetine in the mice model of nerve ligation injury.
Methods: The experiments were conducted in male ICR mice (25-35 g).
To create the neuropathic mouse model, the left L5 and L6 spinal nerves were gently isolated and ligated tightly with 6-0 black silk.
The tactile allodynia was measured with von Frey Filaments using the up-down method. To determine whether the drug interaction between Dexmedetomidine and Paroxetine is additive or synergistic, an equal dose ratio isobolographic analysis was performed. ( Dexmedetomidine 1, 3, 8, 25 μg/kg, Paroxetine 0.6, 2, 6, 20 mg/kg, intraperitoneal)
Results: Intraperitoneal Dexmedetomidine and Paroxetine alone produced a dose-dependent reduction of tactile allodynia.
A Dexmedetomidine-Paroxetine combination produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction after the coadministration of Dexmedetomidine and Paroxetine.
Conclusions: Intraperitoneally administered Dexmedetomidine or Paroxetine produced dose-dependent antiallodynia.
Antiallodynic effect of intraperitoneal Dexmedetomidine, when combined with intraperitoneal Paroxetine, is synergistic in a mice model of nerve ligation injury.
We could suggest the synergistic interaction may be caused by sedation and drowsiness. Therefore, we have to take care when coadministration of both drugs.