Big conductance calcium-activated potassium channel openers control spasticity without sedation.

ABSTRACT:

Background and purpose

Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity.

Experimental approach

Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans.

Key results

VSN16R had nanomolar activity

SUBMITTER: Baker D 

PROVIDER: S-EPMC5522996 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature