Anticonvulsant Properties of Procaine, Cocaine, Adiphenine and Related Structures.

Abstract

Five compounds-procaine hydrochloride, cocaine hydrochloride, adiphenine (Trasentine), beta-(o-benzyl-phenoxy)-gamma-diethylamino-ethane, and Parpanit-the chemical structures of which have a dialkylaminoalkyl linked via O, N or C to an aryl or aralkyl radical, were tested in mice for neuro-toxicity and for ability to modify maximal electroshock seizures. In addition, procaine, cocaine, and Trasentine were tested for ability to modify maximal Metrazol seizures and to prevent postictal depression (anticoma effect). For comparison, 2 compounds (diethylaminoethanol and Antrenyl), the chemical structures of which only partially comply with the above structural prerequisites, were tested only for neurotoxicity and for ability to modify maximal electroshock seizures. Results were as follows: 1. Procaine, cocaine, and Trasentine prevent the tonic-extensor component of maximal electroshock seizures in non-toxic doses and exert an anticoma effect in doses near the toxic level. All 3 agents prevent the tonic-extensor component of maximal Metrazol seizures, but only in doses which frequently synergize with the convulsant to cause death. 2. All compounds tested, the chemical structure of which contains a dialkylaminoalkyl linked via O, N or C to an aryl or aralkyl radical, exhibited anticonvulsant activity. In contrast, diethylaminoethanol and Antrenyl were devoid of anticonvulsant activity. 3. Data indicate that compounds within this series share a common anticonvulsant nucleus, but further studies will be necessary to characterize precisely its structural requirements. 4. The laboratory search for congeners with less transient anticonvulsant action and higher protective index is warranted.