Clinical trial NCT00921765: Reversal of Ketamine Pharmacodynamic Effects With Naloxone
Official title: Naloxone Block of Low-dose (Analgetic Dose) Ketamine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pain
Keywords: Pain
Naloxone
Ketamine
Third Molar
Surgery
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2009-06-16
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallell Group design should be used when final dose had been found
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain intensity (0-10 Numerical Rating Scale)
timeFrame: 30 minutes
Secondary outcomes:
measure: Subjective measurement of psychotomimetic effects
timeFrame: 30 minutes
measure: Adverse effects
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Ullevaal University Hospital
Study officials:
affiliation: University of Oslo
name: Olav Hustveit, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Oslo
name: Elena Landari, DDS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD. Kappa-opioids produce significantly greater analgesia in women than in men. Nat Med. 1996 Nov;2(11):1248-50. doi: 10.1038/nm1196-1248.
citation: Hustveit O, Maurset A, Oye I. Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. doi: 10.1111/j.1600-0773.1995.tb01041.x.
citation: Mathisen LC, Skjelbred P, Skoglund LA, Oye I. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain. 1995 May;61(2):215-220. doi: 10.1016/0304-3959(94)00170-J.
citation: Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1992 Mar;260(3):1209-13.