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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Hello321 on July 1, 2016, at 10:30:25
Im wondering about how strongly meds bind to certain receptors. I dont know if someone on psychobabble might understand how to read the number values for Pimavanserin and Cyproheptadine with the 5ht2a and 5ht2c receptors listed on their Wikipedia pages:
https://en.wikipedia.org/wiki/Cyproheptadine#Overdose
https://en.wikipedia.org/wiki/Pimavanserin
And is there any way to tell which has a stronger effect on the 2a and 2c reveptors at the doses given?
It does say on the Pimavanserin page that its lower number indicated for the 2c receptor means it has lower affinity comoared to the 2a receptor that it shows a higher number for. But that goes against what ive read, that the lower numbers mean theyre actually stronger at those receptors.
Posted by TriedEveryMedication on July 1, 2016, at 13:01:24
In reply to Measuring Drugs Activity at Receptors, posted by Hello321 on July 1, 2016, at 10:30:25
Lower Ki number means stronger binding affinity. Single digit affinities or less are very strong.
here is a sampling of ki's for cyproheptadin
looks like the 2A range is averaging from 1.5 on up, depending on the study and what part of the brain they tested
2c: around 12.
Unfortunately, this DB doesn't have data for Pimavanserin
Posted by Hello321 on July 1, 2016, at 16:07:36
In reply to Re: Measuring Drugs Activity at Receptors » Hello321, posted by TriedEveryMedication on July 1, 2016, at 13:01:24
Interesting website. I was just going by whats listed on Wikipedia for these 2 meds. Wiki showed Pimavanserin to have the stronger binding affinity at both receptors, and hopefully that is correct. But i like that website. Thanks a lot!
Posted by linkadge on July 2, 2016, at 8:41:05
In reply to Re: Measuring Drugs Activity at Receptors, posted by Hello321 on July 1, 2016, at 16:07:36
Yeah, lower Ki means higher receptor affinity for a particular concentration of the drug (i.e. more active at that receptor).
The best site for Ki is:
http://kidbdev.med.unc.edu/databases/pdsp.php
However, one must also consider the factors affecting concentration of the drug namely:
- dose level
- half life
- absorption
- metabolismI.e. a drug with low absorbtion and / or high metabolism, would need a higher dose to achieve a certain concentration.
Linkadge
Posted by linkadge on July 2, 2016, at 9:02:00
In reply to Measuring Drugs Activity at Receptors, posted by Hello321 on July 1, 2016, at 10:30:25
Hi,
According to the site I posted,
Cyrproheptadine (5-ht2c ki) ~ 12
Suprisingly this site doesn't yet have data on pimavanserin. However, if the Wikipedia data is correct, it has a much lower ki (thus higher affinity).
Pimavanserin (5-ht2c ki) ~ 0.44
Now, the real thing you are interested in is the ratio of affinities between different receptors.For example (5-ht2c/5-ht2a ratio)
Cyproheptadine = 12 / 2.5 = ~ 5. In other words it is 5 time more active at 5-ht2a than 5-ht2c.
However,
Pimavanserin = 0.44 / 0.087 ~ 5. So, similarly, it too, is approximately 5 times more active at 5-h2a than 5-ht2c.
If you are looking for something to selectively block 5-ht2c, than these drugs may not be the best options. However, if you had to choose between the two (on paper) I'd select pimvanserin, mainly because it has lower affinity for dopamine, histamine etc. Cyproheptadine is fairly dirty in the sense that it binds to dopamine, adrenaline, calcium channels, histamine etc, in the same range as 5-ht2a/c.
Really, the ratio is more important, because, even if the Ki is high, you could take more drug. However, in the case of cyproheptadine, higher doses would also hit other receptors.
On paper, pimavanserin looks interesting. I currently take mirtazapine (mainly for sleep) however, it hits histamine pretty hard. It might be nice to try a more selective 5-ht2a/c antagonist, to see how it augments venlafaxine with possibly less sedation.
Linkadge
Posted by SLS on July 2, 2016, at 11:36:45
In reply to Re: Measuring Drugs Activity at Receptors, posted by linkadge on July 2, 2016, at 9:02:00
> On paper, pimavanserin looks interesting. I currently take mirtazapine (mainly for sleep) however, it hits histamine pretty hard. It might be nice to try a more selective 5-ht2a/c antagonist, to see how it augments venlafaxine with possibly less sedation.
Adding some nortriptyline to venlafaxine would take care of the 5-HT2a/c receptor antagonism and promote more NE reuptake inhibition than what a low dosage of venlafaxine does.
Understanding that my treatment responses in the past have been modest at best, I was impressed with the combination of venlafaxine + nortripyline. This occurred at a dosage of 75 mg/day of nortriptyline. We now know that I need 150 mg/day. For me, should I need to jettison Parnate, the first thing I would try would be a combination of venlafaxine 300 mg/day + nortriptyline 150 mg/day.
- Scott
Posted by linkadge on July 2, 2016, at 18:01:49
In reply to Re: Measuring Drugs Activity at Receptors » linkadge, posted by SLS on July 2, 2016, at 11:36:45
Hi SLS,
Yeah nortriptyline isn't bad. I tried it by itself (in doses up to 50mg). I was sensitive to some of the effects at this dose.
It was a really good antidepressant, however above 50mg, I noticed some creative dulling and irritability. However, it was very good for anhedonia.
Venlafaxine and remeron are still a very solid combo for me. Remeron helps me sleep at doses as low as 1mg.
Unfortunately coming off remeron, I get really fragmented sleep and frequent awakenings. This could be lithium too.
I'm currently taking 4 meds (or at least prescribed 4 meds). Effexor, remeron, methylphenidate and lithium. I'd like to reduce this to just 3 meds. Perhaps nortriptyline could replace remeron and methylphenidate.
Linkadge
Posted by Hello321 on July 4, 2016, at 15:56:46
In reply to Re: Measuring Drugs Activity at Receptors, posted by linkadge on July 2, 2016, at 9:02:00
Thanks for the info. Much appreciated. Yeah I stumbled upon an article about pimavanserin a few days ago and think it's a very interesting med. I have hopes it's much more potent action could be of benefit after Cyproheptadine lost its effectiveness for me. But its a new med approved specifically for psychosis experienced by those with Parkinson's, which is far from my diagnosis.
I saw online the price for it is at least $1,000, and I don't see Pimavanserin anywhere on my Insurances Drug Formulary :/
I suppose they'd prefer not to pay the high price for it. Have you (or anyone that reads this) had experience with trying to get their health insurance to cover a med that's not listed on their Formulary for an off label treatment? Lol it sounds like a difficult process if it's at all possible they would end up covering it.
Posted by SLS on July 4, 2016, at 16:21:51
In reply to Re: Measuring Drugs Activity at Receptors » linkadge, posted by Hello321 on July 4, 2016, at 15:56:46
Re: Pimavanserin
Very interesting drug. It is now being considered for the maintenance phase of schizophrenia. I will be interested to see what becomes of it.
- Scott
Posted by Hello321 on July 5, 2016, at 13:32:02
In reply to Re: Measuring Drugs Activity at Receptors » linkadge, posted by Hello321 on July 4, 2016, at 15:56:46
Just found that the makers of Pimavanserin offer a 30 day free trial, if anyone else is interested in asking their doc about trying this med.
Posted by Ruuudy on July 7, 2016, at 18:02:31
In reply to Re: Measuring Drugs Activity at Receptors, posted by Hello321 on July 5, 2016, at 13:32:02
It seems they can pinpoint which neurochemicals might be suspected to be having issues. This cool site had some nifty quizzes & information:
http://bebrainfit.com/balance-neurotransmitters/I suffer from dysthymia disorder superimposed with MDD, OCD, and anxiety, but haven't had a MDD in at least 10 years.
I've been taking fluoxetine for 26 years, and been adding clonazepam .5mg for the past few years.The first quiz, Dr. Eric Bravermans Brain Deficiency Quiz, http://www.pathmed.com/uploads/6/4/1/3/64134895/brain_quiz.pdf, gave me results of Dopamine being the main culprit, closely followed by Seratonin.
Interesting little diddy!
Rudy
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