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Optimal novel molecule for high pro-sexual effects with minimal CNS stimulation—chemsex candidates?

B

balea

Bluelighter
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Nov 10, 2014
Messages
55
As the title suggests, I have explored the effects of stimulants like speed and 3-CMC. Among them, 3-CMC exhibited strong pro-sexual properties for me but also significant CNS stimulation and dopaminergic activity.

the goal is to explore the possibility for a novel molecule that maximizes pro-sexual effects while minimizing CNS stimulation and dopaminergic activity. How would you approach this? What pharmacological strategies or structural modifications would be ideal?

Looking forward to your insights and innovative designs!

Some studies

Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder - PMC

Hypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov


Drugs and sexual desire - Wikipedia

en.m.wikipedia.org en.m.wikipedia.org



Drugs with the Side Effect - Hypersexuality

Amantadine , Apomorphine , Aripiprazole , Bromocriptine , Cabergoline , Carbidopa , Entacapone , Lisuride , Morphine , Pramipexole , Rasagiline , Ropinirole , Rotigotine , Tolcapone

@paracelsius? any input? I did see that you have discussed aminorex based substances?

​

 
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I'm reminded that flibanserin (Addyi) recieved a GSL although it's effacacy is questionable.

There are a number of medications that list hypersexuality as a side-effect BUT it's important to note that in ecach case, it's a side-effect and only affects a minority of patients.

Heck, people tell me methamphetamine is prosexual but I just couldn't see it. Too busy having an anxiety attack and suffering acute paranoia to really note such details.
 
Depressant Prosexual Drugs: Alcohol, GHB, GBL, 1,4-BDO.

Stimulant Prosexual Drugs: Meth, LSD, Adderall. (when coming down)
 
Bremelanotide.

Again, if memory serves the effacacy of the stuff is questionable.

I seem to recall it was discovered while developing an anrtifial tanning agent.

I'm of the opinion that almost all of the medications for HSDD were discovered as side-effects of a medication and as such the action is not well understood.

That technology transfer is far more common than people tend to think. If memory serves the first generation of antidepressants were originally developed to treat TB. The second generation was developed on the basis that early antihistamines also had antidepressant properties. In fact, it was only the third generation that was a clean-sheet design and I remain unconvinced that they are better. Safer certainly, but better, no.
 
Dopamine agonists produce extremely unpleasent side-effects. Modulating the release and reuptake of dopamine is generally how dopamagenic medications work. It's only certain serious neurological conditions that make dopamine agonists a reasonable option.
 
The side effects from dopamine agonists are no more unpleasent than dopamine antagonists. I've taken both pramipexole and cabergoline. No dystonic reactions, no jaw spasms, no loss of libido, no weight gain, no anhedonia, etc etc
 
One person is not a statistically valid sample. You can say you didn't suffer side-effects, but you cannot reaonably assert that it automatically extends to everyone else.

The most prominent side-effect of dopamine agonists is nausea with vomiting although diziness and hallucinations appear to be very common. Of course, an animal model won't discover those issues. There are others, I've limited myself to the psychomimetric side-effects. Physical side-effects MAY be detected in animal models - I'm uncertain if they were, but in theory at least, they could be.
 
The agents i have in my folder for female sexual arousal is: Bremalanotide, Flibanserin, PF-219,061, SUN 8399, UK-414,495.

The agents i have for erectile dysfunction include: Aviptadil, Delequamine, DQ-2777, FR 121196, GPI 1485, Moxisylyte, PNU-14277E, SCH-51866.

The agents that I have for premature ejaculation are: Dapoxetine & UK-390,957.
 
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4DQSAR said:
One person is not a statistically valid sample. You can say you didn't suffer side-effects, but you cannot reaonably assert that it automatically extends to everyone else.

The most prominent side-effect of dopamine agonists is nausea with vomiting although diziness and hallucinations appear to be very common. Of course, an animal model won't discover those issues. There are others, I've limited myself to the psychomimetric side-effects. Physical side-effects MAY be detected in animal models - I'm uncertain if they were, but in theory at least, they could be.
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The same goes for you

You said "dopamine agonists produce extremely unpleasant side effects"

Some people tolerate them quite well and the non ergot agonists such as pramipexole have been used with success to treat resistant depressives
 
Smyth2 said:
The agents i have in my folder for female sexual arousal is: Bremalanotide, Flibanserin, PF-219,061, SUN 8399, UK-414,495.

The agents i have for erectile dysfunction include: Aviptadil, Delequamine, DQ-2777, FR 121196, GPI 1485, Moxisylyte, PNU-14277E, SCH-51866.

The agents that I have for premature ejaculation are: Dapoxetine & UK-390,957.
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dear mr Smyth the second,

I have little knowledge on this particular topic, but by accident I stumbled upon a substance referred to as pt-141. Maybe this has potential to add to your folder. It believe it has benefits for the arousal of both male and female, but I think more for females. Anyway, I hope this may be of interest to you.

kind regards,

G.
 
Conky said:
You said "dopamine agonists produce extremely unpleasant side effects"

Some people tolerate them quite well and the non ergot agonists such as pramipexole have been used with success to treat resistant depressives
Click to expand...

Given that dopamine agonists are primarily prescribed to treat serious neurological disorders, side-effects are accepted rather than tolerated (in the medical sense of the term). These side-effects tend to increase over time even if the dose regime isn't modified. Quality of life is the outcome saught by consultants and so careful titration is employed. It's a class of drug where the theraputic window narrows over time. While this is true for many classes of medication, dopamine agonists appear to represent one of the more extreme examples. Of the people I know who take such medications, every one of them has their treatment monitered by a consultant and as far as I know, there is a medication review every three months. But given that they were totally disabled without medication, they seem to accept the multiple side-effects.

It's interesting that they are used in patients with treatment resistant depression. I think it worth considering that depression may be a symptom of a disorder rather a disorder in it's own right. In fact, neurological disorders may manifest as mood disorders. I was aware that newer dopamine agonists are used in low doses for the symptomatic treatment of RLS but again, is RLS the disorder or merely how a neurological disorder manifests?

I admit it's a long time since I read about this class of medication but I'm under the impression that some medications classed as dopamine agonists also have affinity for serotonin and norepinephrine receptors which MAY be involved in their having antidepressant activity. I'm fairly sure the precise reason they are effective in some patient's isn't fully understood. That's not uncommon as human depression is hard to model in animal studies. But here in the UK at least, I don't think dopamine agonists are indicated for depression although as a DLR, consultants are granted the freedom to prescribe a medication 'off-label'. It's certainly an uncommon option.

It's worth remembering that almost every class of antidepressant was discovered by accident. The MAOIs were discovered as resarchers sought a better medication to treat tuburculosis. Tricyclic antidepressants were discovered as researchers explored the QSAR of antipsychotics. SSRIs were developed from first-generation (CNS penetrating) antihistamines and once it was recognized that modulation of monoamines could modify mood, compounds that acted on multiple classes of monoamine were developed. Quite a few psychoactive medications were observed to have antidepressant effects and became adopted (sometimes in modified forms - presumably to optimize them for their new role). In at least some of these cases, it's questionable if the primary illness is major depression or if another disorder manifests as a mood disorder.

I have only ever used generalities as each person will have a unique reaction to a medication. But by the term 'some people', do you have a specific indication, medication and dose-regime in mind?

I don't know if you read the book 'The Case of the Frozen Addicts' but I presume you are aware of the story. There was mention of the fact that Barry Kidston began to abuse the very medication he was prescribed to treat the profound Parkinson's he had suddenly developed. What the book doesn't state is what medication was involved. Do you have any idea what it could have been? I don't think it could have been a dopamine agonist. In the book, the suicide of Barry Kidson is also related in slightly clouded terms. It states that he intentially overdosed on cocaine while sat under a tree on the Berkley(?) campus. I'm wondering if it was intentional or if he was consuming cocaine as a form of self-medication. I mention this last detail because I remember a study from the 1950s in which a dopamine releaser was compounded with an antipsychotic medication which to me sounded like an odd concept Maybe the dopamine releaser was intended to mitigate the side-effects of the antipsychotic? I don't know/
 
4DQSAR said:
Given that dopamine agonists are primarily prescribed to treat serious neurological disorders, side-effects are accepted rather than tolerated (in the medical sense of the term). These side-effects tend to increase over time even if the dose regime isn't modified. Quality of life is the outcome saught by consultants and so careful titration is employed. It's a class of drug where the theraputic window narrows over time. While this is true for many classes of medication, dopamine agonists appear to represent one of the more extreme examples. Of the people I know who take such medications, every one of them has their treatment monitered by a consultant and as far as I know, there is a medication review every three months. But given that they were totally disabled without medication, they seem to accept the multiple side-effects.

It's interesting that they are used in patients with treatment resistant depression. I think it worth considering that depression may be a symptom of a disorder rather a disorder in it's own right. In fact, neurological disorders may manifest as mood disorders. I was aware that newer dopamine agonists are used in low doses for the symptomatic treatment of RLS but again, is RLS the disorder or merely how a neurological disorder manifests?

I admit it's a long time since I read about this class of medication but I'm under the impression that some medications classed as dopamine agonists also have affinity for serotonin and norepinephrine receptors which MAY be involved in their having antidepressant activity. I'm fairly sure the precise reason they are effective in some patient's isn't fully understood. That's not uncommon as human depression is hard to model in animal studies. But here in the UK at least, I don't think dopamine agonists are indicated for depression although as a DLR, consultants are granted the freedom to prescribe a medication 'off-label'. It's certainly an uncommon option.

It's worth remembering that almost every class of antidepressant was discovered by accident. The MAOIs were discovered as resarchers sought a better medication to treat tuburculosis. Tricyclic antidepressants were discovered as researchers explored the QSAR of antipsychotics. SSRIs were developed from first-generation (CNS penetrating) antihistamines and once it was recognized that modulation of monoamines could modify mood, compounds that acted on multiple classes of monoamine were developed. Quite a few psychoactive medications were observed to have antidepressant effects and became adopted (sometimes in modified forms - presumably to optimize them for their new role). In at least some of these cases, it's questionable if the primary illness is major depression or if another disorder manifests as a mood disorder.

I have only ever used generalities as each person will have a unique reaction to a medication. But by the term 'some people', do you have a specific indication, medication and dose-regime in mind?

I don't know if you read the book 'The Case of the Frozen Addicts' but I presume you are aware of the story. There was mention of the fact that Barry Kidston began to abuse the very medication he was prescribed to treat the profound Parkinson's he had suddenly developed. What the book doesn't state is what medication was involved. Do you have any idea what it could have been? I don't think it could have been a dopamine agonist. In the book, the suicide of Barry Kidson is also related in slightly clouded terms. It states that he intentially overdosed on cocaine while sat under a tree on the Berkley(?) campus. I'm wondering if it was intentional or if he was consuming cocaine as a form of self-medication. I mention this last detail because I remember a study from the 1950s in which a dopamine releaser was compounded with an antipsychotic medication which to me sounded like an odd concept Maybe the dopamine releaser was intended to mitigate the side-effects of the antipsychotic? I don't know/
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By some people I was mostly talking about my previous experiences taking dopamine agonists as well as literature I've read that indicates they are relatively safe and well tolerated when used in the treatment of hyperprolactinemia induced by antipsychotics. If dose reduction isn't practical. Adjunctive aripiprazole, cabergoline, and bromocriptine were used from what I've read. Cabergoline appears to be the most effective and I would start with 0.25mg and see how I feel over the next few days before deciding I need a second weekly dose. Bromocriptine I would start at 1.25mg in the morning and go from there. I would not use aripiprazole.

Regarding the compounded antipsychotic/dopamine releaser, the effects of the latter would be greatly reduced by the former. It would have to be used seperately at much higher doses and even then there would be very limited CNS effects. I used high doses of methamphetamine while on haloperidol and it helped normalize side effects like the severe anhedonia but it was totally inaffective for hyperprolactinemia symptoms. I never got high on the meth even after consuming hundreds of mgs in one sitting.
 
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