PK563217M is a highly selective ligand for the dopamine D7 receptor, Ki 4.2nM at the cloned human receptor. GTP gamma S binding establishes it as a full agonist. It has a clean profile of activity against other dopamine receptors (>500nM); the nearest activity is at D4 (230nM), and no significant interaction with serotinergic, adrenergic, noradrenergic, muscarinic, cholinergic or histamine receptors. The bioavailability of PK563217M is 27% in rat (half-life 5 hours) and 38% in dog (half-life 8 hours). No significant toxicological effects were observed during 28 days dosing in rat and dog at doses below 75mg/kg. PK563217M was formulated in a gel capsule with starch filler for first human dosing
Subjects were recruited from undergraduates of ****** University Medical School and were medically and psychologically profiled before dosing. Subjects were scheduled to receive 5mg capsules of PK563217M for 5 consecutive days, followed by 9 days washout and 2 x 5mg capsules for 5 consecutive days. The individual responses to the initial dosing are reported below.
Samples were taken from the subjects at 30-minute intervals and indicate that PK563217M achieved peak plasma levels 1 hour post dosing with a mean half-life of 10 hours.