Progress Report from the Testing Program for Stimulant and Depressant Drugs (1993)

Preclinical abuse potential assessment of the anticonvulsant zonisamide

“…Although this partial suppression may have been due to some cross-dependence with pentobarbital, similar suppression of behavioral signs has been observed for other drugs, such as the tricyclic antidepressant amitriptyline and the competitive N-methyl-D-aspartate antagonist (cis-4-phosphomethyl)-2-piperidinedicarboxylic acid [Patrick et al, 1994], which failed to suppress weight loss and also failed to show signs of dependence liability in drug self-administration or drug discrimination studies. Since the observable signs of barbiturate withdrawal are excitatory in nature (e.g., increased response to stimulation, aggressive postures), drugs such as zonisamide with acute depressant effects could be expected to attenuate some of these signs.…”

“…Previous studies have shown that many depressant drugs that are recognized as having dependence-producing properties prevent the loss of body weight in this procedure. Included among these are pentobarbital itself (e.g., the data included in this report), most available benzodiazepines such as brotizolam, alprazolam, bromazepam, nordiazepam, temazepam, and midazolam [Patrick et al, , 1986[Patrick et al, , 1992Yutrzenka et al, 1989] and other sedativehypnotic drugs such as methaqualone [Yutrzenka et al, 1990. ] The correlation between suppression of the weight loss in this procedure and dependence liability in humans seems high.…”

“…During the substitution and withdrawal phases of the experiment a number of observations were made to assess signs of withdrawal in the rats [Patrick et al, 1994]. For all rats, body weight and overt signs of hyperexcitability were determined at 8 and 24 h each day and following changes in the infusate.…”