LY344864 is a selective receptor agonist with an affinity of 6 nM (K _i ) at the recently cloned 5-HT1F receptor. It possesses little affinity for the 56 other serotonergic and non-serotonergic neuronal binding sites examined. When examined for its ability to inhibit forskolininduced cyclic AMP accumulation in cells stably transfected with human 5-HT1F receptors, LY344864 is shown to be a full agonist producing an effect similar in magnitude to serotonin itself.

After an intravenous dose of 1 mg/kg, rat plasma LY344864 levels decline with time whereas brain cortex levels remaine relatively constant for the first 6 hours after injection. Oral and intravenous LY344864 administration potently inhibit dural protein extravasation caused by electrical stimulation of the trigeminal ganglion in rats. Co-injection of LY 344864 and systemically ineffective doses of METH significantly decreases preference scores and the rewarding properties of METH during the reinstatement phase. In addition, administration of LY 344864 has no effect on the acquisition of CPP in rats.