Amitriptyline and Clomipramine Increase the Concentration of Administered L-Tryptophan in the Rat Brain

Abstract

The tricyclic antidepressant amitriptyline has been shown to reduce concentrations of large neutral amino acids (LNAA) in rat plasma. Compounds with that property might interact with such amino acids used as therapeutic agents with a central site of action by causing a change in the relationship between the administered LNAA and its endogenous LNAA competitors for carrier-mediated transport through the blood-brain barrier into the brain. This study was performed to investigate if the antidepressant agents amitriptyline and clomipramine could, by such a mechanism, increase brain concentrations of administered tryptophan. Intraperitoneal administration of L-tryptophan alone (100 mg kg-1) resulted in an increase in the concentration of tryptophan in the rat brain from 14 +/- 0.7 to 100 +/- 4.3 nmol g-1 compared with rats given saline only. When rats were given tryptophan with amitriptyline (25 mg kg-1, i.p.) or clomipramine (25 mg kg-1, i.p.) brain concentrations of tryptophan were increased even further, to 150 +/- 4.5 and 157 +/- 10.2 nmol g-1, respectively. Administration of L-tryptophan alone resulted in an increase in the rat plasma tryptophan ratio [(concentration of tryptophan)/(total concentration of LNAAs)] from 0.14 +/- 0.003 to 0.42 +/- 0.011 compared with rats given saline only. When rats were given tryptophan with amitriptyline or clomipramine the plasma tryptophan ratios were increased even further to 0.52 +/- 0.017 and 0.54 +/- 0.025, respectively. All these effects were statistically significant (P < 0.001). These findings support the hypothesis that tricyclic antidepressants could interact with administered tryptophan by changing the relationship in plasma between tryptophan and its endogenous LNAA competitors for transport into the brain, resulting in higher concentrations of tryptophan in the brain. It is possible that this could be the mechanism of the previously reported finding that clomipramine and tryptophan potentiate each other in the treatment of depression.

Conversion of L-Tryptophan into Melatonin Is the Possible Action Pathway Involved in the Effect of L-Tryptophan on Antidepressant-Related Behavior in Female Rats: Analysis of the Influence of Treatment Duration

“…In the same species, the reduction of immobility by TRP in Porsolt's swim test has been also reported suggesting that TRP has antidepressant-like properties [45]. In rats, the reduction of depression by L-TRP alone or in association with clomipramine [46] or fluoxetine [47] was clearly demonstrated. The present work is also in accordance with some studies using acute TRP depletion in association to depression-related behavior in rodents.…”

Role of food-drug interactions in neurological and psychological diseases

“…Therefore, consumption of high fiber foods, including legumes, fish, meat, and vitamin C-rich foods, may cause a decrease in the absorption of amitriptyline (Ismail 2009). TCAs may also cause a decrease in the plasma tryptophan concentration and an increase in the concentration of tryptophan in the brain (Eriksson and Walinder 1998). Low plasma tryptophan values have been observed after only six months after treatment (Fekkes et al 1997).…”

“…It may decrease in the plasma tryptophan concentration and an increase in the concentration of tryptophan in the brain. Eriksson andWalinder 1998 Fekkes et al 1997 It may increase body weight by stimulating hunger and increasing carbohydrate consumption and also influencing the energy balance.…”

Duck cerebellum participates in regulation of food intake via the neurotransmitters serotonin and neuropeptide Y

“…Administration of L-tryptophan increases brain 5-HT concentrations, a mechanism by which L-tryptophan suppresses food intake. [8][9][10][11][12][13][14][15] Serotonin exerts its diverse physiological actions through different receptor subtypes (5-HT1-5-HT7). 16 Lorcaserin, a 5-HT2C receptor agonist, reduces food intake in rats that is reversed by pre-treatment with the 5-HT2C selective antagonist, SB 242084.…”