EVALUATION OF ADCI AGAINST CONVULSANT AND LOCOMOTOR STIMULANT EFFECTSOF COCAINE - COMPARISON WITH THE STRUCTURAL ANALOGS DIZOCILPINE AND CARBAMAZEPINE

Both the antiepileptic, carbamazepine, and the N-methyl-D-aspartate re ceptor antagonist, dizocilpine, have shown preclinical efficacy agains t behavioral and toxic effects of cocaine. Nonetheless, side effects o r toxicity of these compounds either alone or in conjunction with coca ine are problematic. 0,11-dihydro-5h-dibenzo[a,d]cyclohepten-5,10-imin e (ADCI), a molecular hybrid of these compounds, has been shown to hav e a broad anticonvulsant profile with a good protective index (behavio ral TD50/anticonvulsant ED(50)). In male Swiss Webster mice, ADCI and dizocilpine produced dose-dependent protection against the convulsant effects of cocaine that were insensitive to carbamazepine. However, in contrast to dizocilpine, ADCI did not produce behavioral impairment o n the inverted screen test demonstrating a protective index of greater than 15; the protective index for dizocilpine was 1.2. All three comp ounds attenuated the locomotor stimulant effects of cocaine without si gnificantly decreasing locomotor activity on their own, although the c ocaine antagonism was not always dose dependent. Only dizocilpine incr eased spontaneous locomotor activity when given alone and augmented th e locomotor stimulant effects of cocaine. The results confirm the nove l anticonvulsant activity of ADCI and its lack of phencyclidine-like b ehavioral side effects. The data also suggest a modest blocking action of these compounds against the locomotor stimulatory effects of cocai ne.