5 replies to this topic

[BigJohn]

I am taking a herbal supplement called Cissus Quadrangularis for my tendonitis. I read the label, which states that this herbal supplement is cannot be used in conjunction with MAO B inhibitors. Cissus Quadrangularis has been shown to affect serotonin. Would using this supplement be safe with racetams? Do racetams show any potential to be MAO-B inhibitors? 

 

Thanks for your insight!

[datrat]

No known MAO-B inhibition from any of the racetams. Not sure why they advised against MAO-B inhibition with cissus if it only affects serotonin as MAO-B doesn't work on serotonin. I've used cissus while taking seligiline (MAO-B inhibitor) without any problems.

[Area-1255]

No known MAO-B inhibition from any of the racetams. Not sure why they advised against MAO-B inhibition with cissus if it only affects serotonin as MAO-B doesn't work on serotonin. I've used cissus while taking seligiline (MAO-B inhibitor) without any problems.

You are correct, MAO-B degrades dopamine and Phenylethylamine not serotonin, MAO-A on the other hand degrades norepinephrine, dopamine and serotonin. COMT and MAO-A are very similar because of this - but brain regions may differ. MAO inhibition tends to produce peripheral effects as well, but when degraded the chances of getting serotonin syndrome increase greatly.

Because 80% of you won't look to see every herb you are taking and the possible, even indirect effects on serotonin that 3 or 4 nutraceuticals you are taking may have - it is very risky for any inexperienced user who doesn't have a thorough knowledge of pharmacology/pharmacodynamics to mess with.

 

Also interactions with these enzymes are incredibly diverse - and hormones have a large effect on MAO.

For example, free brain testosterone after converting into estrogen - inhibits MAO enzymes as well as cAMP-Phosphodiestearase.

Estrogen also increases opioid and endorphin release in the hypothalamus. Estrogen has effects on various serotonin receptor subtypes.

Estrogen acts as an antagonist at 5-HT3 receptors (which produce nausea), thus in low-moderate (but not high) concentrations, brain E2 can be a technical anti-emetic. Estrogen upregulates and activates 5-HT2(A) and 5-HT2© receptors, and as such can contribute to psychosis and potentiation of psychodelics (again, moderate not high concentration).

Estrogen allows prolactin release by 5-HT4, but may have overall some dopaminergic properties by not only influencing D(2) like expression, but also by downregulating 5-HT1A receptors which are involved greatly in many neuroendocrine responses and act as serotonin autoreceptors; decreasing serotonin feedback / release through a presynaptic mechanism.

 

However, 5-HT1A serotonin receptors have different POST SYNAPTIC functions; inhibiting histamine, glutamate, acetylcholine, nitric oxide and GABA - especially in the MPOA (Medial Preoptic Area) and PVN (Paraventrical Nucleus). It is thought to be both the modulation of D2 receptors, the 5-HT1A antagonist effect of estradiol and the alpha blockade potential that allows for both an anti-depressant effect and pro-libido effect by estrogen metabolites.

Estradiol induces expression of 5-hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 receptor messenger ribonucleic acid in rat anterior pituitary cell aggregates and allows prolactin release via the 5-HT4 receptor.

 

http://www.medscape....rticle/406718_2

 

 

 

Estrogen affects concentrations of other neurotransmitters and neuromodulators as well. It competitively inhibits the enzyme that inactivates norepinephrine, thus providing a stimulatory effect similar to that of many antidepressant medications.^[39] Like pharmaceutical monoamine oxidase (MAO) inhibitors, estrogen reduces MAO activity, resulting in higher levels of both catecholamines and serotonin in the brain.^[40] Estrogen also increases opioid and endorphin production by the hypothalamus.^[41]

 

 

 

http://hyper.ahajour...t/35/1/262.full

http://www.pnas.org/...8/8517.full.pdf

 

 

 

Estradiol inhibits smooth muscle cell growth; however, the mechanisms involved remain unclear. Because estradiol stimulates cAMP synthesis and adenosine inhibits cell growth, we hypothesized that the conversion of cAMP to adenosine (ie, the cAMP-adenosine pathway) mediates in part the inhibitory effects of estradiol on vascular smooth muscle cell growth. To test this hypothesis, we examined the effects of estradiol (0.001 to 1 μmol/L) on serum-induced DNA, collagen, and total protein synthesis and cell number in the absence and presence of 1,3-dipropyl-8-p-sulfophenylxanthine (10 nmol/L; A₁/A₂ adenosine receptor antagonist), KF17837 (10 nmol/L; selective A₂ adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (10 nmol/L; selective A₁ adenosine receptor antagonist), and 2′,5′-dideoxyadenosine (10 μmol/L; adenylyl cyclase inhibitor). Estradiol inhibited all measures of cell growth, and the concentration-dependent inhibitory curves for estradiol were shifted to the right (P<0.05) by 1,3-dipropyl-8-p-sulfophenylxanthine, KF17837, and 2′,5′-dideoxyadenosine but not by 8-cyclopentyl-1,3-dipropylxanthine. Moreover, the inhibitory effects of estradiol were enhanced by stimulation of adenylyl cyclase with forskolin and by inhibition of adenosine metabolism with erythro-9-(2-hydroxy-3-nonyl)adenine plus iodotubericidin (adenosine deaminase and kinase inhibitors, respectively). Estradiol also increased levels of cAMP and adenosine, and these effects were blocked by 2′,5′-dideoxyadenosine (P<0.05). Our results support the hypothesis that estradiol stimulates cAMP synthesis and cAMP-derived adenosine regulates smooth muscle cell growth via A₂ adenosine receptors. Thus, the cAMP-adenosine pathway may contribute importantly to the antivasooclusive effects of estradiol. 

Edited by Area-1255, 01 September 2014 - 11:18 PM.

[Area-1255]

http://www.uaq.mx/qu... et al 2011.pdf

 

Estradiol increases the anorexia associated with increased 5-HT2C receptor activation in ovariectomized rats

[BigJohn]

thanks guys!

[3AlarmLampscooter]

In my experience very few clinicians are aware of the difference between MAO-B inhibitors and MAO-A inhibitors, and will generally tread very cautiously when it isn't always necessary.