in rhesus monkeys: When responding was stable, dimethocaine (0.030-1.7 mg/kg/ infusion) was substituted for the cocaine training dose. Dimethocaine administration produced higher response rates compared with that of procaine, and was a more potent reinforcer. Drug effects on behavior were related to DAT occupancy in monkey striatum during neuroimaging with positron emission tomography (PET). DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 66 and 82% and <10-41% for doses of dimethocaine and procaine that maintained maximum response rates, respectively. Acute administration of dimethocaine (10-40 mg/kg, IP) significantly increased locomotor activity and time spent on the drug-paired side and reduced the relative number of entries and time spent on the open arms of the plus-maze in mice.

Dimethocaine showed full displacement of [3H]2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1.5-naphthalenedisulfonate (CFT) binding (0-30 microM tested) and full inhibition of dopamine uptake (0-100 microM tested). Dimethocaine was only slightly less potent than cocaine with an estimated Ki of 1.4 micorM and an IC50 value of 1.2 microM for [3H]CFT binding and dopamine uptake.