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hi CB,

So how much similarity is there expected to be within the -done class and the -pine class?  I'm assuming that there has to be some level of chemical similarity for the generics to sound so similar.  But I hadn't really heard it mentioned before.  I'm just curious because my new one is a -done (iloperidone - fanapt), and I had good results with risperdal (risperidone) before I got EPS but an absolutely god awful time with latuda (lurasidone).  So I'm not sure if it's hit or miss or what exactly.

my prior pdoc also wanted to try me on fanapt (we didn't at the time because I landed in the hospital first and then he wanted to stick with what they'd tried).

I think the new one might be beneficial if some sleep-related issues get sorted out.  But I was just curious about things like side effect profile/how they work etc.  I'm not good at understanding receptors and such things.

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I have done well on all the "pine" AP's I've tried (Seroquel, clozaril, Zyprexa) unfortunately I gain too much weight on them. 

The "done" class have all given me EPS or Akathisia but little weight gain if any. 

I really like vraylar so far, I don't know if it is in the same class as the other ones.  I am hoping I can stay on it for the long term.  It's both energizing and calming at the same time.  I've  never experienced that before with an AP. 

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@browri will likely be able to explain this better than I will.

The "-pines" tend to be lower potency antipsychotics (lower Daffinity antagonism), have more potent antihistamine, more potent anticholinergic, and have more potent antiadrenergic properties. What this means is higher doses needed for efficacy (with the exception of olanzapine and asenapine [Saphris]); lower propensity for EPS like akathisia; greater propensity for sedation and weight gain; greater propensity for dry mouth, constipation, and blurry vision; and greater propensity for orthostatic hypotension. They generally have high affinity for the 5-HT2A receptor in comparison to the D2 receptor.

The "-dones" tend to be the opposite, with higher potency antipsychotics (higher D2 affinity antagonism); less potent antihistamine if any affinity at all for the H1 receptors; less potent anticholinergic if any affinity at all for the muscarinic acetylcholine receptors; and have less potent antiadrenergic properties. As such, this translates to an opposite side effect profile: lower dosages needed for efficacy; greater propensity for EPS like akathisia; lower propensity for sedation and weight gain; lower propensity for dry mouth, constipation, and blurry vision; and lower propensity for orthostatic hypotension. The "-done" ziprasidone (Geodon) even has SNRI-like properties to it. They generally have high affinity for the 5-HT2A receptor in comparison to the D2 receptor.

The "rips," which include aripiprazole (Abilify), brexpiprazole (Rexulti), and cariprazine (Vraylar), are a class to themselves. I don't exactly know how to classify them except that they are all dopamine partial agonists. Abilify and Rexulti are preferentially D2 partial agonists, whereas Vraylar is preferentially a D3 partial agonist. They have very high affinity for these receptors, and generally actually have higher affinity for them than the 5-HT2A receptors, making them very "atypical" for atypical antipsychotics. They are purported to cause less EPS like akathisia, but we all know that is not the case for most people with Abilify and Vraylar... They are purported to cause less weight gain, but that is a YMMV thing... People may lose weight, maintain weight, or gain tons of weight on these meds. Some are stimulated, some are sedated, and for some these meds are neutral. Generally, they don't have much antiadrenergic effects, save for Rexulti. No anticholinergic effects to speak of, nor much antihistaminergic effects.

EDIT: The "two pips and a rip..." Thanks @browri!

@browri, please help me out here! lol.

Edited by mikl_pls
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It's even simpler that that.

"-pines" -- most other activities are stronger than their activity at D2 receptors (serotonin, histamine, muscarinic acetylcholine, etc.) and the highest serotonin:dopamine activity ratio of all the atypicals.

"-dones" -- fewer activities (relative to the pines) at other receptors that are stronger than D2 but still stronger serotonergic activity than dopamine overall. The only exception to that in this class is Latuda (lurasidone). Arguably, ziprasidone and lurasidone can be broken down into their own "class" separate from risperidone, paliperidone, or iloperidone.

"two pips and a rip" (aripiprazole, brexpiprazole, and cariprazine) have affinity for D2 receptors that exceeds their activity at almost all other receptors. So brexpiprazole for example, the only receptor where it has an even stronger affinity than D2 (0.3nM) is 5HT1A (0.12nM). Few if any other receptor activities while have an affinity that exceeds that of D2

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On 10/22/2018 at 8:27 PM, dancesintherain said:

hi CB,

So how much similarity is there expected to be within the -done class and the -pine class?  I'm assuming that there has to be some level of chemical similarity for the generics to sound so similar.  But I hadn't really heard it mentioned before.  I'm just curious because my new one is a -done (iloperidone - fanapt), and I had good results with risperdal (risperidone) before I got EPS but an absolutely god awful time with latuda (lurasidone).  So I'm not sure if it's hit or miss or what exactly.

my prior pdoc also wanted to try me on fanapt (we didn't at the time because I landed in the hospital first and then he wanted to stick with what they'd tried).

I think the new one might be beneficial if some sleep-related issues get sorted out.  But I was just curious about things like side effect profile/how they work etc.  I'm not good at understanding receptors and such things.

Good luck with the fanapt dances! Maybe the -dones are your kinda med (minus the latuda, of course).

Like you, I had decent to pretty good results with risperidone and paliperidone for psychosis for me (but always with another AAP on board).

And latuda, forget about that one! I had a god awful time with that med too. Manic, psychotic, forced IP, it wasn’t a pretty sight. I got up to 160 mg I believe before having to be placed IP and put back on seroquel ASAP. No way will I touch that one again with a ten foot pole. 

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16 hours ago, gb84 said:

I have done well on all the "pine" AP's I've tried (Seroquel, clozaril, Zyprexa) unfortunately I gain too much weight on them. 

The "done" class have all given me EPS or Akathisia but little weight gain if any. 

I really like vraylar so far, I don't know if it is in the same class as the other ones.  I am hoping I can stay on it for the long term.  It's both energizing and calming at the same time.  I've  never experienced that before with an AP. 

Those -pine meds you listed are the exact meds I have done well on too. It is quite unfortunate that they cause so much weight gain. I had gained 100 lbs then I lost some weight with the help of my dr. I still have a long way to go but every little bit helps. 

I wish the -done meds helped me. They just don’t control my symptoms as much by far. 

I’m glad to hear vraylar is going so well for you! I almost wish I would have tried that one first instead of the clozapine. But it is so expensive. I don’t know if we could have afforded it, unfortunately. There are so many issues with the clozapine for me so far. It better be worth it in the long run. But I digress. 

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5 minutes ago, Wonderful.Cheese said:

Those -pine meds you listed are the exact meds I have done well on too. It is quite unfortunate that they cause so much weight gain. I had gained 100 lbs then I lost some weight with the help of my dr. I still have a long way to go but every little bit helps. 

Actually the "-pines" did really well for me too. However, I've found that Rexulti (brexpiprazole) is actually a really good substitute. It has caused some weight gain but nothing like olanzapine.

While brexpiprazole only has one serotonergic activity that is greater than its dopaminergic activity, it still is VERY strong at serotonin receptors. One of the things that is pretty standard for the "pines" and "dones" is 5HT2A is always stronger than D2, but in the case of brexpiprazole, 5HT2A is an affinity of 0.47nM where D2 is only SLIGHTLY stronger at 0.3nM. Aripiprazole on the other hand 5HT2A is 3.4-35nM to its D2 of 0.74-0.9nM. So brexpiprazole KINDA OF breaks the mold and behaves more like a "done" or a "pine" in that it has potent anxiolytic and antidepressant effects.

 

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1 hour ago, browri said:

It's even simpler that that.

"-pines" -- most other activities are stronger than their activity at D2 receptors (serotonin, histamine, muscarinic acetylcholine, etc.) and the highest serotonin:dopamine activity ratio of all the atypicals.

"-dones" -- fewer activities (relative to the pines) at other receptors that are stronger than D2 but still stronger serotonergic activity than dopamine overall. The only exception to that in this class is Latuda (lurasidone). Arguably, ziprasidone and lurasidone can be broken down into their own "class" separate from risperidone, paliperidone, or iloperidone.

"two pips and a rip" (aripiprazole, brexpiprazole, and cariprazine) have affinity for D2 receptors that exceeds their activity at almost all other receptors. So brexpiprazole for example, the only receptor where it has an even stronger affinity than D2 (0.3nM) is 5HT1A (0.12nM). Few if any other receptor activities while have an affinity that exceeds that of D2

Thanks @browri! :D 

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4 minutes ago, browri said:

Actually the "-pines" did really well for me too. However, I've found that Rexulti (brexpiprazole) is actually a really good substitute. It has caused some weight gain but nothing like olanzapine.

While brexpiprazole only has one serotonergic activity that is greater than its dopaminergic activity, it still is VERY strong at serotonin receptors. One of the things that is pretty standard for the "pines" and "dones" is 5HT2A is always stronger than D2, but in the case of brexpiprazole, 5HT2A is an affinity of 0.47nM where D2 is only SLIGHTLY stronger at 0.3nM. Aripiprazole on the other hand 5HT2A is 3.4-35nM to its D2 of 0.74-0.9nM. So brexpiprazole KINDA OF breaks the mold and behaves more like a "done" or a "pine" in that it has potent anxiolytic and antidepressant effects.

 

Interesting. I will have to keep that one in mind in case clozapine gets to be too much. It’s good to know that it has effects on anxiety and depression too.  Does it also prevent mania? That would be a wonder drug! 

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12 hours ago, Wonderful.Cheese said:

Interesting. I will have to keep that one in mind in case clozapine gets to be too much. It’s good to know that it has effects on anxiety and depression too.  Does it also prevent mania? That would be a wonder drug! 

You mean does rexulti? EH. I kno some have had success for mania but usually as an adjunct. Didn't help me to the point we switched to Vraylar 

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9 hours ago, Iceberg said:

You mean does rexulti? EH. I kno some have had success for mania but usually as an adjunct. Didn't help me to the point we switched to Vraylar 

Agreed. It does have mood stabilizing action, but on it's own?.....this is why I take Depakote as well.

Edited by browri
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