The concentrations of orphenadrine and its N-demethylated derivatives in rat brain, after intraperitoneal administration of orphenadrine and tofenacine

As an extension of a previous investigation into the effect of orphenadrine and tofenacine on the concentration and binding of 5-hydroxytryptamine (5HT) in rat brain, the concentrations of orphenadrine and/or its N-demethylated derivatives in rat brain were determined at various intervals after intraperitoneal administration of either tritiated orphenadrine hydrochloride or tofenacine hydrochloride. Thin-layer chromatography of brain extracts showed that both drugs attain their maximal concentration in brain within 15 min after administration. Following orphenadrine dosage, tofenacine was also found in the brain, the maximum concentration occurring after 45–60 min. A slight amount of N,N-didemethyl orphenadrine was only found after tofenacine had been administered. Apparently both orphenadrine and tofenacine penetrate rapidly into the brain. From comparison of the present data with the previous ones on the effect of these drugs on 5HT brain concentrations it is presumed that in the case of both drugs, a two-pool system is involved. One of the pools would be a slowly equilibrating one, directly linked to the storage of 5HT, whereas the other would be a rapidly equilibrating pool.