Tryptophan drug interactions

MDMA TRYPTOPHAN Tryptophan administration produces poor therapeutic response and adverse effects as passage across the blood-brain barrier is impaired in users and ex-users Tiyptophan t amount of precursors of serotonin Avoid concomitant use >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

The risk of serotonin syndrome may be increased shortly after dosage increases of SSRIs or when drug interactions increase serotonin activity. Concomitant or proximal use of SSRIs, tricyclic antidepressants, or monoamine oxidase inhibitors may cause serotonin syndrome. Further, the addition of certain drugs, such as tryptophan, dextromethorphan, cocaine, or sympathomimetics, to SSRI therapy may increase the risk of developing serotonin syndrome." ... 

The interactions of many important drugs, metabolites, and structurally related compounds with HSA have been char-acterized on the basis of their inhibition of its acetylation by p-nitrophenyl acetate. Dissociation constants of 10 5M or lower have been determined for tryptophan, phenylpyru-vate, several pharmacologically important benzodiazepines, several types of small, apolar, anionic drugs and related compounds that interact specifically with the inhibitory site. Two other classes of inhibitory compounds have been identified and similarly characterized, the members of which interact either to a comparable extent or preferentially with one other site. The inhibitory site appears to be elongated, apolar, and has a monoanion binding site near one end. 

These studies provide evidence for at least four binding sites in HSA one for tryptophan, that also interacts strongly with many other compounds one that appears to be very specific for bilirubin one high-affinity site for palmitate and one high-affinity site for warfarin, indomethacin, phenylbutazone, and a number of other drugs (i.e. see Ref. 36). Each of these sites appears to be separate and distinct from each of the others. 

There is now the acknowledgment that nutritional factors are indeed being studied for their role in combating mental problems. Thus, for example, a review article in the scientific literature by Kathleen M. Kantak titled Nutritional Aspects of Drug Action on Behavior, cited in the Bibliography, is representative. In this instance, the effects of (pure) tryptophan, magnesium/vitamin Bg, and vitamin C were examined, alone or in combination with drugs. There was an interaction even for such mental illnesses as schizophrenia, depression, autism, and hyperactivity. 

Fig. 24.8 HOMOs and LUMOs calculated using AMI for complexes formed between ethylindole representing tryptophan and fourtruncated drug molecules. Charge-transfer interactions may occur in complexes 1,2 and 3 they are impossible in complex 4.

A man with sehizophrenia taking tryptophan, lorazepam, vitamin C, ben-zatropine and nicotinic acid, developed a severe urticarial rash covering his faee, neek and trunk 3 days after starting clozapine 150 mg daily. All of the drugs except lorazepam were stopped, and the rash subsided. It did not recur when clozapine was restarted, even at a dose of 600 mg daily, nor when small doses of benzatropine and fluphenazine were briefly added. The authors draw the inference that tryptophan, vitamin C and nicotinic acid may have been responsible for this alleged interaction with clozapine. ... 

The manufacturers of duloxetine contraindicate the concurrent use of MAOIs because of the theoretical risk of the serotonin syndrome. Similarly they recommend caution with other serotonergic drugs, including the SSRIs, venlafaxine, and tryptophan. Fluvoxamine should not be used with duloxetine, because it markedly increases duloxetine levels. Low-dose paroxetine caused a modest increase in the duloxetine ATJC, and fluoxetine is predicted to interact similarly. 

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