Will we synthesise any dramatically new drugs in the future?

[serotonin2A]

It should be easy to find the drug you are thinking about by reading through the list of schedule I opioids, but there aren't any compounds on the list that fit your description. It sounds like you might be talking about 14-phenylpropoxymetopon or something like that but those potent compounds were never tested in humans, so no one has any clue if they produce substantial euphoria.

If such a drug had been discovered then it would have resulted in a large research program. Scientists are very interested in the neural substrates for euphoria. Pharmaceutical companies are also interested, because they have always wanted to figure out how to make opioids that do not produce euphoria, to make painkillers with less abuse liability.

There are a few opioids that were used medically but found to be prone to abuse and then pulled off the market. But none of those compounds were engineered to be especially potent, and they are just typical opioids that happen to be more euphoric than most other opioid painkillers.

 

[CrazyEngineer]

I get the rest of your suggestions, I think.. But why would anyone want to antagonize Melatonin receptors?

The goal of orexin agonism (and melatonin antagonism) is to create drugs that let you stay awake and alert without resorting to serotonin/norepinephrine/dopamine agonism or reuptake inhibition (with all the wonderful side effects that creates). We already know that melatonin metabolism directly effects people's circadian rhythms; a couple of milligrams will induce a fairly nice natural feeling sleepiness within 20-30 minutes without a lot of the euphoriant or addictive effects of GABA-A agonists/PAMs like barbiturates and benzodiazepines. Similarly, research on orexin pathways indicates that deficiencies in orexin concentrations (or orexin receptor insensitivity/damage) results in narcolepsy; there's already a new drug out on the market (suvorexant, brand name Belsomra) that works by antagonizing your orexin receptors.

Now, the inverse of that process (melatonin antagonism or inverse agonism (if that's possible, I don't know) and orexin agonism) would prolong alertness and wakefulness simply by blocking the neurological signals your body uses to induce sleep and priming the receptor systems that actively promote wakefulness. There's no way of telling for sure, but in theory molecules that did that would be able to produce stimulant effects without any of the euphoria, jitters, cardiotoxicity, or other side effects that come with taking more traditional stimulants (amphetamines, cocaine, phenidates). You'd finally have a fairly safe wake-up pill with (presumably) a minimal tolerance profile.

 

[rakketakke]

Common sense tells me that we can only produce drugs that are already analogous to chemicals used by the brain. It's not possible to create a chemical to have specifically tailored effects on the brain if the brain doesn't already use a similar pathway. The brain wouldn't have any mechanism for binding/receiving it. However, it should absolutely be possible with more specific and detailed knowledge of drug/receptor pharmacology to be able to create an analogue drug with very specific actions - possible entirely eliminating undesired effects while maximising therapeutic ones.

We have already done this to some extent. There is an opiate whose name currently eludes me, that was designed to express ALL major molecular factors that determine how strong an opiate will be. This drug was quite quickly banned, and is not discussed much at all - even among researchers. Why? It can simply be swallowed, yet produce a way more intense and long-lasting rush than heroin. It's so addictive that it couldn't be used even as medicine. This is completely different from simply using very potent opioids like fentanyl derivatives. Those allow you to use much less of the drug and may bind tightly, but still produce a ceiling effect when it comes to subjective euphoria. This drug apparently is not like that, and directly activates the brain's pleasure centers extremely powerfully and persistently. It would completely and disastrously hook anyone who took it, no matter what the purpose. Of course knowing this, I obviously want to try it even though I should know better; nothing good could possibly come of it.

We only discovered the GHB receptor after synthesis and ingestion.

Perhaps more of these chemicals will arise in the future and with proper research more receptors will be found?

 

[nAON]

We only discovered the GHB receptor after synthesis and ingestion.

Perhaps more of these chemicals will arise in the future and with proper research more receptors will be found?

I think (I can't pull up any citations on this) most of the recent discoveries have been as a result of genomics rather than pharmacology. Though of course that doesn't mean they have any idea wtf the receptor does, just that something that looks like a receptor is probably being expressed somewhere.

 

[ex-amine]

in my humble opinion it might be better to change the question around : "Are there any drug effects that have not been discovered yet ?"... Then the drug to induce this might be discovered in the near to very far future..
To name a few :
- perpetual tip of the tongue
- understanding language subconsciously but not able to utter it ( kinds blindsighted but with speech)
- various sleeping paralysises
- oscilating pitch movements in sound perception
- instant and enduring goosebumps
- prominent lucid dreaming
- multipletude synesthesia

All these can occure in the brain, therefore it's reasonable that there might be substances or combinations of These that might induce this..

So i think we still have a long and very interesting way ahead of us.

Your Ex