Comparison of central nervous system actions of taurine and N-pivaloyltaurine.

N-Acetyl, N-propionyl, and N-pivaloyl derivatives of taurine were synthesized by applying a modified Schotten-Bauman method starting from taurine and using the corresponding acid chloride or acid anhydride for direct acylation reactions. The central nervous system actions of these lipid soluble taurine derivatives, which were presumed to pass the blood-brain barrier, were studied and compared to those of taurine in mice. A large dose (15 mmol/kg) of intraperitoneally administered taurine lengthened the pentobarbitone induced sleep by 30%. N-Pivaloyltaurine was 45 times more potent but not more effective than taurine. Neither N-acetyl- nor N-propionyltaurine lengthened the pentobarbitone induced sleep in doses up to 3 mmol/kg. Intraperitoneally administered N-pivaloyltaurine depressed the locomotor activity in a smaller dose and for a longer period than taurine. However, when administered intracerebroventricularly neither N-acetyl- nor N-pivaloyltaurine altered the locomotor activity in three times larger dose than in which taurine clearly depressed it. Intraperitoneally administered N-pivaloyltaurine decreased the rectal temperature slightly more than taurine, whereas intracerebroventricularly administered taurine was clearly more potent in inducing hypothermia than its acyl derivatives. Intraperitoneally administered N-pivaloyltaurine was about three times more potent than taurine in increasing the striatal concentration of dopamine. Intraperitoneally administered N-pivaloyltaurine only in a very large dose (3 X 15 mmol/kg) slightly and transiently increased the cerebral taurine concentration. Carboxylesterase inhibition by bis-p-nitrophenyl phosphate (BNPP) did not modify this increase. Furthermore, BNPP pretreatment modified neither the hypothermic nor the striatal dopamine concentration elevating effects of N-pivaloyltaurine. Our results suggest that N-pivaloyltaurine possesses taurine-like pharmacological actions. It is not converted to taurine to produce these actions. When administered intracerebroventricularly it is less potent than taurine. However, when administered intraperitoneally it is more potent than taurine because it seems to pass the blood-brain-barrier more easily than taurine. Thus N-pivaloyltaurine could be used to study the behavioural and other central nervous system actions of taurine.