gamma-Carbolines: a novel class of cannabinoid agonists with high aqueous solubility and restricted CNS penetration.

Article Details

Citation

Cheng YX, Pourashraf M, Luo X, Srivastava S, Walpole C, Salois D, St-Onge S, Payza K, Lessard E, Yu XH, Tomaszewski MJ

gamma-Carbolines: a novel class of cannabinoid agonists with high aqueous solubility and restricted CNS penetration.

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1619-24. doi: 10.1016/j.bmcl.2011.12.124. Epub 2012 Jan 4.

PubMed ID
22284817 [ View in PubMed
]
Abstract

An oral, peripherally restricted CB1/CB2 agonist could provide an interesting approach to treat chronic pain by harnessing the analgesic properties of cannabinoids but without the well-known central side effects. gamma-Carbolines are a novel class of potent mixed CB1/CB2 agonists characterized by attractive physicochemical properties including high aqueous solubility. Optimization of the series has led to the discovery of 29, which has oral activity in a rat inflammatory pain model and limited brain exposure at analgesic doses, consistent with a lower risk of CNS-mediated tolerability issues.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DronabinolCannabinoid receptor 1Ki (nM)10N/AN/ADetails
DronabinolCannabinoid receptor 1EC 50 (nM)17N/AN/ADetails
DronabinolCannabinoid receptor 2Ki (nM)24N/AN/ADetails