Posted by undopaminergic on April 22, 2008, at 10:04:01
In reply to Re: Question For Scott » bulldog2, posted by SLS on April 19, 2008, at 15:13:16
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> > Also at lower doses is there less chance of a hypertensive crisis if I eat the wrong foods.
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> In reality, it depends on the percentage of MAO being inhibited in the gut. I don't happen to know what the threshold is for reducing the tyramine reaction.
>Probably the worst thing to do with regard to minimising the inhibition of gut and liver MAO is to take a single large oral dose of a MAOI, as that would lead to the highest concentrations of the inhibitor precisely in the gut and liver, before the drug is absorbed into the blood stream and greatly diluted.
Since the type A isoform of MAO predominates in the gut, MAO-B preferring inhibitors are less effective at increasing sensitivity to dietary tyramine. However, the subtype selectivity of MAOIs is dose-dependent.
Transdermal and sublingual absorption can be used to reduce exposure of gut/liver MAO to the inhibitor, while maintaining efficacy and possibly reducing the effective dose - especially in the case of highly metabolised MAOIs such as selegiline. Divided oral doses should theoretically reduce gut drug concentration in comparison with a single oral dose.
Co-administration of noradrenaline reuptake inhibitors (NRIs) reduces the sensitivity to tyramine that has been absorbed into the blood stream. In the selection of a NRI, it's important to avoid those also potently inhibiting serotonin reuptake. There is a shortage of information available on this strategy, due to long-standing fears that this combination might precipitate serious hypertensive reactions.
There is some evidence that the slow-acting rasagiline-derived MAOI (and acetylcholinesterase inhibitor) ladostigil can be taken orally without significantly affecting gut MAO while achieving high degrees of brain MAO-A and -B inhibition. Of course, this compound is still only available as the raw active ingredient.
Finally, it should be noted that there are differences in individual vulnerabilites. In studies using the 12 mg/24 h selegiline patch, 3 people (of 11) had significant (>30 mmHg) hypertensive responses to 25 mg doses of oral tyramine, whereas some required well over 90 mg. Co-administration of food increased the effective dose of tyramine by more than 100 mg. According to the same source (EMSAM prescribing info), a high-tyramine meal contains up to 40 mg.
poster:undopaminergic
thread:823248
URL: http://www.dr-bob.org/babble/20080420/msgs/824770.html