Adrenocorticotropin release is not involved in the nicotine-induced reversal of hemorrhagic shock in anesthetized rats.

In a model of volume-controlled hemorrhagic shock causing the death of all control animals within 30 min, the intravenous injection of nicotine produced a rapid, sustained and dose-dependent restoration of cardiovascular and respiratory functions, with 60 and 100% survival 2 h after the administration of 3 and 12 micrograms/kg, respectively. An effect similar to that of the highest dose of nicotine were obtained with the intravenous bolus injection of ACTH(1-24) at the dose of 160 micrograms/kg. However, the ACTH plasma levels of hemorrhage-shocked rats treated with nicotine was not different from that of hemorrhage-shocked rats treated with saline, thus excluding the possibility that nicotine-induced shock reversal may be due to the massive release of ACTH. Since in rats pretreated with cycloheximide at a dose (20 mg/kg intraperitoneally) causing an 82% inhibition of protein synthesis, and then bled to hemorrhagic shock, the effect of nicotine was greatly reduced (only the dose of 50 micrograms/kg producing 100% survival 2 h after treatment), protein synthesis, however, seems to be important for the effect of nicotine in hemorrhagic shock, at least at the lowest doses.

Pharmacokinetics of tiaprofenic acid after oral administration in fasting patients during and between migraine attacks.

This study examined the pharmacokinetics of 300 mg of tiaprofenic acid, a NSAID belonging to the 2-arylpropionic class, as a single oral dose, in 10 migraine patients during and out of migraine attacks. Plasma concentration of tiaprofenic acid was determined by HPLC analysis. Drug absorption appeared to be the same during and out of migraine attacks (absorption half life: during attack, 0.249 +/- 0.122 hr; out of attack, 0.249 +/- 0.105 hr; maximum plasma concentration: during attack, 37.8 +/- 9.8 ug/ml; out of attack, 40.1 +/- 13.2 ug/ml). The other pharmacokinetic parameters evaluated were not affected by headache attacks as well. We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks. Also, our data suggest that tiaprofenic acid might be useful in the treatment of migraine.