In the past drugs such as cocaine were considered primarily stimulants and local anaesthetics.
Today as we have developed a more comprehensive understanding of neurotransmission in all its extraordinary complexity, cocaine has now been classified as much more than an exotic stimulant or effective local anaesthetic, and has now been recognised as a rather unique type of drug, with a number of potentially therapeutic effects and acting upon more than just our CNS.
Cocaine is now classified as an 'SSNDRI' and is without a doubt the best known of the SSNDRI's or "Selective Seretonin,Noradrenaline, Dopamine Re-uptake Inhibitor" drugs.
These compounds have a range of effects including antibiotic and anti-inflammatory actions, and the race to synthesize a non-toxic active variant has been going now for just over 10yrs. One of the issues being these drugs appear to be highly addictive
The other main problem is so far many of the synthetic compounds have been shown to be highly toxic with some having an LD50 of <100mg/kg
It's a complex 'problem' but whoever does successfully 'solve it' and produce a 'safe' compound/s for therapeutic use will likley make huge profits.
That's assuming they DO proper trials, so that 10years down the track folks don't start dropping from something like heart disease (which happened with Vioxx, a cox-2 inhibitor, with many similarities to this compound)
this is a very good wiki page on the effects of all 3 of these NT and neurotransmission in general. It explains a lot about how these NTs work alone and/or in combination to affect our moods.
http://en.wikipedia.org/wiki/Serotonin%E2%80%93norepinephrine%E2%80%93dopamine_reuptake_inhibitor
There's still much to know, but we've come a hell of a long way in the last few decades, learning 'more' in the last 20 years or so had in the previous 200! Especially with our newfound understanding of 'genomics', and the advent of " fMRI's ".
In fact the spread of MRIs around the world (and other new analytical equipment) have been giving scientists and medicos ways to 'see and understand things', like brain functions in real time, or the virtually 'instant' analysis of specimens via advances with technology, knowledge and equipment, which was only 'dreamt about' as recently as the late 1980's has advanced our understanding of the human body and medicine in general. (and the 'tricorder's' definitely in the pipeline somewhere!)
Fascinating stuff, As long as I have NO doubt these will become the Rxd drug of the future, once they find a 'safe' synthetic variation of these compounds they can patent!
Here's SSNDRI # 2: Hyperforin. It's a drug first isolated in 1975 and the first synthesis was only published in 2010, so it's a fairly new drug, to the pharmaceutical database but one that has been used for centuries because 'apparently' it's the principal active compound in St John's Wort.
Although it contains significant amounts of hyperforin, there is still much debate over the 'mechanism' of St John's Wort.
http://en.wikipedia.org/wiki/Hyperforin http://en.wikipedia.org/wiki/St_John%27s_wort
Hyperforin is one of the few other known as well as the only other known 'naturally occurring' SSNDRI's
It is one of the main active constituents found in St John's wort It might be quite useful as an adjuvant enhancing the effects of other compounds, it actually has an unusually wide range of properties, including anti-inflammatory, anxiolytic and antibiotic actions!
"Hyperforin has antibiotic properties and is active against methicillin-resistant strains of Staphylococcus aureus (MRSA)" this factor alone makes it unique in the world of antibiotics and is currently badly needed, (MRSA=MutipleResistant Staphylococcus Aureus)
Very interesting, hey salat what's the word on St John's wort?
I've heard in can have some major interactions with quite a few other drugs? It seems to have a reputation as being a good anti-depressant, but what other things IS it good for?
With all the properties attributed it (St John's Wort) and due to containing this compound, it's currently being considered for treating almost everything, from infections and farts, to ADHD and schizophrenia!)
It does however sound rather promising
I think?
Hyperforin has antibiotic properties and is active against methicillin-resistant strains of Staphylococcus aureus (MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 ?g/mL, as well as against other gram-positive bacteria. Which is highly significant in itself!
Looks like there's going to be a whole new class of compounds on the way...not sure how I feel about this?
Today as we have developed a more comprehensive understanding of neurotransmission in all its extraordinary complexity, cocaine has now been classified as much more than an exotic stimulant or effective local anaesthetic, and has now been recognised as a rather unique type of drug, with a number of potentially therapeutic effects and acting upon more than just our CNS.
Cocaine is now classified as an 'SSNDRI' and is without a doubt the best known of the SSNDRI's or "Selective Seretonin,Noradrenaline, Dopamine Re-uptake Inhibitor" drugs.
These compounds have a range of effects including antibiotic and anti-inflammatory actions, and the race to synthesize a non-toxic active variant has been going now for just over 10yrs. One of the issues being these drugs appear to be highly addictive
Quote
"Cocaine is a short-acting SNDRI that also exerts auxiliary pharmacological actions on other receptors. Cocaine is a relatively "balanced" inhibitor, although facilitation of dopaminergic neurotransmission is what has been linked to the reinforcing and addictive effects. In addition, cocaine has some serious limitations in terms of its cardiotoxicity due to its local anesthetic activity. Thousands of cocaine users are admitted to emergency units in the USA every year because of this; thus, development of safer substitute medications for cocaine abuse could potentially have significant benefits for public health.
Many of the SNDRIs currently being developed have varying degrees of similarity to cocaine in terms of their chemical structure. There has been speculation over whether the new SNDRIs will have an abuse potential like cocaine does. However, for
pharmacotherapeutical treatment of cocaine addiction it is advantageous if a substitute medication is at least weakly reinforcing because this can serve to retain addicts in treatment programmes:
... limited reinforcing properties in the context of treatment programs may be advantageous, contributing to improved patient compliance and enhanced medication effectiveness.
However, not all SNDRIs are reliably self-administered by animals. Examples include:
PRC200-SS was not reliably self-administered.
RTI-112 was not self-administered because at low doses the compound preferentially occupies the SERT and not the DAT.
Tesofensine was also not reliably self-administered by human stimulant addicts.
The nocaine analog JZAD-IV-22 only partly substituted for cocaine in animals, but produced none of the psychomotor activation of cocaine, which is a trait marker for stimulant addiction"
The other main problem is so far many of the synthetic compounds have been shown to be highly toxic with some having an LD50 of <100mg/kg
It's a complex 'problem' but whoever does successfully 'solve it' and produce a 'safe' compound/s for therapeutic use will likley make huge profits.
That's assuming they DO proper trials, so that 10years down the track folks don't start dropping from something like heart disease (which happened with Vioxx, a cox-2 inhibitor, with many similarities to this compound)
this is a very good wiki page on the effects of all 3 of these NT and neurotransmission in general. It explains a lot about how these NTs work alone and/or in combination to affect our moods.
http://en.wikipedia.org/wiki/Serotonin%E2%80%93norepinephrine%E2%80%93dopamine_reuptake_inhibitor
There's still much to know, but we've come a hell of a long way in the last few decades, learning 'more' in the last 20 years or so had in the previous 200! Especially with our newfound understanding of 'genomics', and the advent of " fMRI's ".
In fact the spread of MRIs around the world (and other new analytical equipment) have been giving scientists and medicos ways to 'see and understand things', like brain functions in real time, or the virtually 'instant' analysis of specimens via advances with technology, knowledge and equipment, which was only 'dreamt about' as recently as the late 1980's has advanced our understanding of the human body and medicine in general. (and the 'tricorder's' definitely in the pipeline somewhere!)
Fascinating stuff, As long as I have NO doubt these will become the Rxd drug of the future, once they find a 'safe' synthetic variation of these compounds they can patent!
Here's SSNDRI # 2: Hyperforin. It's a drug first isolated in 1975 and the first synthesis was only published in 2010, so it's a fairly new drug, to the pharmaceutical database but one that has been used for centuries because 'apparently' it's the principal active compound in St John's Wort.
Although it contains significant amounts of hyperforin, there is still much debate over the 'mechanism' of St John's Wort.
http://en.wikipedia.org/wiki/Hyperforin http://en.wikipedia.org/wiki/St_John%27s_wort
Hyperforin is one of the few other known as well as the only other known 'naturally occurring' SSNDRI's
It is one of the main active constituents found in St John's wort It might be quite useful as an adjuvant enhancing the effects of other compounds, it actually has an unusually wide range of properties, including anti-inflammatory, anxiolytic and antibiotic actions!
"Hyperforin has antibiotic properties and is active against methicillin-resistant strains of Staphylococcus aureus (MRSA)" this factor alone makes it unique in the world of antibiotics and is currently badly needed, (MRSA=MutipleResistant Staphylococcus Aureus)
Very interesting, hey salat what's the word on St John's wort?
I've heard in can have some major interactions with quite a few other drugs? It seems to have a reputation as being a good anti-depressant, but what other things IS it good for?
With all the properties attributed it (St John's Wort) and due to containing this compound, it's currently being considered for treating almost everything, from infections and farts, to ADHD and schizophrenia!)
It does however sound rather promising
I think? Quote
Pharmacology
Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort. It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine,
and of GABA and glutamate, with IC50 values of 0.05-0.10 mcg/mL for all compounds, with the exception of glutamate, which is in the 0.5 mcg/mL range. Hyperforin also inhibits the reuptake of glycine and choline,. It appears to exert these effects by activating the transient receptor potential ion channel TRPC6. Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake.
Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).
Some pharmacokinetic data on hyperforin is available for an extract containing 5% hyperforin. Maximal plasma levels (Cmax) in human volunteers were reached 3.5h after administration of an extract containing 14.8 mg hyperforin. Biological half-life (t½) and mean residence time were 9h and 12h respectively with an estimated steady state plasma concentration of 100 ng/mL (approx. 180 nM/L) for 3 doses/d. Linear plasma concentrations were observed within a normal dosage range and no accumulation occurred.
Hyperforin has been found to be a potent inhibitor of COX-1 and 5-LO with IC50 values of 0.3?M and 90nM respectively.
Giving it an anti-inflammatory action of approximately 3-18 times stronger than aspirin.
Reuptake Inhibition
Neurotransmitter IC50 (?M)
5-HT 0.205 ± 0.045
Norepinephrine 0.080 ± 0.024
Dopamine 0.102 ± 0.019
GABA 0.184 ± 0.041
L-Glutamate 0.829 ± 0.687
Antibiotic
Hyperforin has antibiotic properties and is active against methicillin-resistant strains of Staphylococcus aureus (MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 ?g/mL, as well as against other gram-positive bacteria. Which is highly significant in itself!
Looks like there's going to be a whole new class of compounds on the way...not sure how I feel about this?