Reversal of Ketamine Pharmacodynamic Effects With Naloxone

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the analgetic and other effects effect of ketamine are partly mediated through opioid receptors

Detailed Description
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Ketamine er et dissociative anaesthetic closely related with phencyclidine (PCP). Phencyclidine is a non-competitive NMDA-antagonist, and it is assumed that the pharmacodynamic mechanism of action for ketamine is the same. Receptor binding studies shows that ketamine has affinity to many receptor types, including opioid mu and kappa receptors. Ketamine has only about 25 times lower affinity for kappa receptors than for the NMDA-receptor complex. Naloxone is a specific antagonist for opioid receptors and block both mu og kappa receptors. A dose of naloxone 10 times larger than required to block mu receptors is required to block kappa receptors. Experiments with naloxone suggest that ketamine is not a mu agonist, but experiments with sufficient large naloxone doses to block kappa receptors have not been carried out in humans.

Official Title
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Naloxone Block of Low-dose (Analgetic Dose) Ketamine

Conditions
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Pain

Intervention / Treatment
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* Drug: Saline
* Drug: Saline + Ketamine
* Drug: Naloxone + Placebo
* Drug: Naloxone + Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females of norwegian Caucasian origin who needs surgical removal of impacted third molars Exclusion Criteria: Anamnestic information regarding psychiatric diagnosis regarding mother/father or brother/sister Concommitant medication other than oral contraceptives Hypersensitivity towards NSAID/opioids/study drugs Females with suspected or confirmed pregnancy Lactating females Surgery lasting more than 60 minutes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallell Group design should be used when final dose had been found
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Placebo<br>Saline single bolus dose iv + saline single bolus dose iv | Drug: Saline<br>* Saline single bolus dose followed by saline single bolus dose iv<br>* Other names: Physiological saline 0.9%;|
| Active Comparator: Placebo + Ketamine<br>Saline single bolus dose followed by single bolus dose of ketamine 0.2 mg/kg bw | Drug: Saline + Ketamine<br>* Single bolus dose of saline followed by ketamine 0.2 mg/kg bw<br>* Other names: ATC code: N01A X03;|
| Active Comparator: Naloxone + Placebo<br>Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline | Drug: Naloxone + Placebo<br>* Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline<br>* Other names: Physiological saline 0.9%;|
| Active Comparator: Naloxone + Ketamine<br>Single bolus dose of ketamine 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw | Drug: Naloxone + Ketamine<br>* Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw<br>* Other names: ATC code: N01A X03;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity (0-10 Numerical Rating Scale) |  | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective measurement of psychotomimetic effects |  | 30 minutes | 
| Adverse effects |  | 30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Naloxone, Ketamine, Third Molar, Surgery