PHARMACODYNAMICS OF PHENOBARBITAL ANESTHESIA AND PENTYLENETETRAZOL-INDUCED MAXIMAL SEIZURES IN A RAT MODEL OF NEOPLASTIC SPINAL-CORD COMPRESSION

The purpose of this investigation was to determine whether paraplegia induced by neoplastic cord compression affects the pharmacodynamics of phenobarbital general anesthesia or of pentylenetetrazol (PTZ)-induce d convulsions. Paraplegic rats harboring a thoracolumbar epidural tumo r, or an identical hindlimb tumor mass, received an i.v. infusion of p henobarbital until the onset of anesthesia. At that point, the phenoba rbital concentrations in the CSF and serum were measured. Similarly, P TZ was infused until the onset of maximal seizures. It was found that changes related to systemic tumor growth and newly developed paraplegi a due to neoplastic spinal cord compression did not attenuate the phar macodynamics of phenobarbital. However, sustained paraplegia of 4 days ' duration reduced CNS sensitivity to the hypnotic action of the barbi turate as evidenced by the higher cerebrospinal fluid phenobarbital co ncentration required to induce anesthesia (170 +/- 31 vs 125 +/- 20 mg /L; P < 0.05). On the other hand, sustained paraplegia did not affect brain threshold concentration for PTZ-induced seizures.