Electroencephalographic and convulsant effects of the delta opioid agonist SNC80 in rhesus monkeys.
Non-peptidic delta opioid receptor agonists are being evaluated for a wide range of clinical applications; however, the clinical utility of piperazinyl benzamide delta agonists such as SNC80 may be limited by convulsant activity. The purpose of the present study was to evaluate the electroencephalographic and convulsant activity produced by a high dose of 10 mg/kg SNC80 IM in rhesus monkeys. EEG and behavioral activity were examined in four adult male rhesus monkeys after IM administration of SNC80. Monkeys were seated in a standard primate restraint chair, and EEG activity was recorded using an array of 16 needle electrodes implanted subcutaneously in the scalp in a bipolar (scalp-to-scalp) montage in a longitudinal direction, with bilateral frontal, central, temporal, and occipital leads. Behavior was recorded using video monitoring equipment. Initially, all monkeys were tested with 10 mg/kg SNC80, which is a relatively high dose 3-10-fold greater than doses necessary to produce a variety of other behavioral effects. Behavioral convulsions and EEG seizures were observed in one of the four monkeys. In this monkey, neither behavioral convulsions nor EEG seizures were observed when a lower dose of 3.2 mg/kg was administered nine weeks later or when the same dose of 10 mg/kg SNC80 was administered one year later. These results suggest that IM administration of SNC80 is less potent in producing convulsant effects than in producing other, potentially useful behavioral effects (e.g. antinociception) in rhesus monkeys.
Danielsson
Ingela
I
Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, NIH, United States; Cyberonics, Houston, TX, USA.
Gasior
Maciej
M
Stevenson
Glenn W
GW
Folk
John E
JE
Rice
Kenner C
KC
Negus
S Stevens
SS
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012640:Seizures / Q000139:chemically induced*
D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide