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Cannabinoid penetration into mouse brain as determined by ex vivo binding
F Petitet1, B Jeantaud, P Bertrand
1Neurochemistry Department, CRVA, Rhône-Poulenc Rorer, Vitry-sur-Seine, France. francois.petitet@rp-rorer.fr
European Journal of Pharmacology
|July 28, 1999
Summary
Brain penetration of cannabinoid receptor ligands was assessed in mice. Natural cannabinoids like delta9-tetrahydrocannabinol showed good brain entry, while some synthetic agonists had poor penetration and short duration of action.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cannabinoid receptor ligands are crucial for understanding the endocannabinoid system.
- Evaluating brain penetration is key to developing effective neurological therapeutics.
Purpose of the Study:
- To assess the brain penetration and duration of action of various cannabinoid receptor ligands in a mouse model.
- To compare the in vivo efficacy of natural cannabinoids, synthetic agonists, and antagonists.
Main Methods:
- An ex vivo binding assay using [3H]WIN 55212-2 on mouse cerebellar membranes was employed.
- Compounds were administered via intraperitoneal or oral routes.
- Pharmacological activity and brain penetration were quantified.
Main Results:
- Natural cannabinoids (methanandamide, delta9-tetrahydrocannabinol) exhibited high brain penetration.
- Synthetic agonists (CP 55940, WIN 55212-2) showed poor brain penetration and limited duration of action (<4 hours).
- The cannabinoid CB1 receptor antagonist SR141716A demonstrated good brain penetration and a prolonged duration of action.
Conclusions:
- Brain penetration varies significantly among cannabinoid receptor ligands.
- Natural cannabinoids and specific antagonists are more effective for brain-targeted cannabinoid therapies.
- Further research into synthetic agonists may be needed to improve their pharmacokinetic profiles.