Possible Interaction: Phenobarbital and Tryptophan

“Chronic administration of morphine, nicotine or phenobarbitone has previously been shown to inhibit rat liver tryptophan pyrrolase activity by increasing hepatic [NADPH], whereas subsequent withdrawal enhances pyrrolase activity by a hormonal-type mechanism.”

“Administration of L-tryptophan at a rate of 0.8 mg/min with phenobarbital was associated with statistically significant reductions in the total dose and concentrations of phenobarbital in serum, serum water, brain, and cerebrospinal fluid (CSF) at onset of LRR.”

“The 0.08 mg/min infusion of L-tryptophan had a less pronounced effect, with statistically significant reductions of phenobarbital concentrations at onset of LRR in brain and CSF.”

“It is proposed that combined administration of phenobarbital and tryptophan leads to substrate stabilisation of tryptophan 2,3-dioxygenase, and that this is accompanied by the binding of the newly synthesised haem, thus making haem unavailable for formation of cytochrome P-450.”

“Significant activation of the holoenzyme was found, when tryptophan was administered 2 h after phenobarbital administration.”

“There was an increase in the amount of cytochrome P-450 within 12 h of administration of a single dose … maintained over the next 12 h. Tryptophan had no effect on the amount of cytochrome P-450, but administration of tryptophan … phenobarbital blocked the increase that … of phenobarbital alone.”

“Administration of both tryptophan and phenobarbital together resulted in even greater stimulation than when the compounds were given alone.”

“In addition, phenobarbital administered either singly or in combination with tryptophan resulted in 80% mortality, which was reduced to zero by pretreatment with cortisol.”

“In normal, as well as in adrenalectomized rats, tryptophan and phenobarbital administered either idividually or together increased microsomal protein concentration.”

“In well-fed normal male rats, either force-feeding of tryptophan or a single injection of phenobarbital produced significant increments in hepatic microsomal cytochrome P-450 and the associated aniline hydroxylase activity.”