Reversal of Ketamine Pharmacodynamic Effects With Naloxone

Pain Clinical Trial

Official title:

Naloxone Block of Low-dose (Analgetic Dose) Ketamine

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00921765
• Other study ID #: DOK-018
• Status: Terminated
• Phase: Phase 4
• First received: June 15, 2009
• Last updated: April 3, 2018
• Start date: December 2009
• Est. completion date: December 2017

Study information

• Verified date: April 2018
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Saline
Saline single bolus dose followed by saline single bolus dose iv
• Saline + Ketamine
Single bolus dose of saline followed by ketamine 0.2 mg/kg bw
• Naloxone + Placebo
Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline
• Naloxone + Ketamine
Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw

Locations

Country	Name	City	State
Norway	Ullevaal University Hospital	Oslo

Sponsors (2)

Lead Sponsor	Collaborator
Ullevaal University Hospital	University of Oslo

Country where clinical trial is conducted

Norway, 

References & Publications (4)

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. — View 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. — View 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):215-20. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain intensity (0-10 Numerical Rating Scale)		30 minutes
Secondary	Subjective measurement of psychotomimetic effects		30 minutes
Secondary	Adverse effects		30 minutes