Cocaine, long a component of Brompton's Cocktail, a mixture used in palliative care to ease suffering in patients with terminal pain has been replaced by other psychostimulants through the years like dexedrine. The idea is that although amphetamines don't produce much analgesia on their own, they potentiate the analgesia of opiates and also decrease sedation that makes it easier to give higher doses. Is there any evidence that cocaine produces any sort of central analgesia in an analogous way. By the way the reference about amphetamines and analgesia is from the 9th addition of Goodman & Gilman's The Pharmacological Basis for Therapeutics on page 219 under the sub heading analgesia it states that"...amphetamine can enhance the analgesia produced by morphine-like drugs." Then it says see chapter 23.
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Cocaine And Central Analgesia
- Thread starter jspun
- Start date
Nagelfar
Bluelight Crew
I don't believe there is any?Cocaine Targets
D(1A) dopamine receptor
Sodium channel protein type 10 subunit alpha
Sodium channel protein type 11 subunit alpha
Sodium channel protein type 5 subunit alpha
Sodium- and chloride-dependent GABA transporter 1
Sodium-dependent noradrenaline transporter
D(3) dopamine receptor
Kappa-type opioid receptor
Sodium-dependent dopamine transporter
Sodium-dependent serotonin transporter
Nagelfar
Bluelight Crew
Interesting. Sodium channel effects indeed must be the the local anesthetic effects. Is this list from the OP source given?Na+ channel inhibition is responsible for local anesthetic effect. 5-HT interneurons have an inhibitory effect on pain perception. Sometimes types of pain respond to ssri, although effect modest. Tramadol inhibits monamine reuptake. Wonder if Cocaine has central analgesic properties and SERT reuptake inhibition basis for this.
Sources are from the Drug Bank database.
Funny thing is that benzocaine (the first local anesthetic with structural similarities to cocaine?) was developed years before the structure of cocaine was known. Look at the cocaine molecule and you'll see the alkanolamine-PhCOOH ester typical to so many local anesthetics.Use as an adjuvant
My question has little to due with the local anaethetic action of the drug, which is well documented, but of the ability of the drug to produce analgesia individually of which there is little influence. However, it may be possible that cocaine potentiates the analgesia caused by other agents, a well documented property of the amphetamines, which have the further therapeutic advatage of decreasing sedation and allowing larger doses of opiate analgesics to be tolerated. This is the rationale for including cocaine in Brompton's Hospital Mixture. But peer-reviewed research has failed to support theurapeutic potential and the rationale for continuing to include it in the historic hospice formulation. Cocaine might have an opioid component in its mechanism of action. Bupe decreases CA self administration (maybe through a K- mediated effect). Also, anectdotally, some dope fiends have reported that coke decreased the severity of withdrawl. Seemed to increase it for me personally. Meth did decrease opiate abstinance syndrome severity for the first couple of hours for me, but then it came back with a vengance. Can anyone think of a reason to keep coke in Brompton's mixture and what would be an appropriate dose taking oral decreased bioavailability into consideration. What other effect of cocaine might make the dying process easier, speculation welcome too.jspun, since you're looking for the mechanism of CIA, which may not be well known, have you looked into the action of NK-1 ligands in the nucleus accumbens? Substance P, it seems, blunts the euphoric effect of opiates but keeps their analgesic properties intact. What's more, substance P doesn't block the pleasurable effects of cocaine and may even mimic some of cocaine's effects in the drug's absence. Two items I've been reading:
http://biologie.kappa.ro/Literature/PDF_Archives/PDF_archive_2001/nature%20rev%20neurosci/2/83.pdf
http://www.find-health-articles.com/rec_pub_19385993-substance-p-cocaine-employ-convergent-mechanisms-depress-excitatory.htm
Nagelfar
Bluelight Crew
The "Sodium-dependent dopamine transporter" & "Sodium-dependent serotonin transporter" now interest me as much as the "kappa" receptor as targets of cocaine in action...
Those two sodium relations to those monoamines may very well be cocaine's 'unique' effect as a local anesthetic to actually mediating the stimulant actions that can't otherwise in difference be sniffed out in research as to why certain ones prefer cocaine over phenyltropanes and the amphetamine/phenethylamines class generally.... Cocaine always seems on top and I still want them to better study the local anesthetic properly when conjoined to its stimulant action closer.... I do think there is something there, may this be it?
I'm not sure what you're referring to when you say "certain ones".
Those proteins are just the run-of-the-mill SERT and DAT.
There's a thorough structural case study on the cocaine molecule vis-a-vis the local anesthetics in the first volume of The Organic Chemistry of Drug Synthesis. You shouldn't have to hunt around too much to find it as a PDF.Seep, I skimed the articles about the ability of substance P to increase availablity of DA in reward centers ( I believe the article mentioned the accumbens). Somehow I would excpect the opposite effect because one associates substance P with aversive stimuli, however maybe thats only spinothalamic mediated pain afferents. Now cocaine and heroin (or opiates in general) seem to have a synergistic effect on magnitude of reinforcement. Wonder how this fits in? My question was about the effect of cocaine an supraspinal analgesia or its use as an adjuvant in pain management. Amphetamines and maybe ritalin (which anecdotally sems to have a more cocaine like subjective effect) is also thought to be an opiate analgesic potentiator. Raised this question because cocaine was a component of "brompton's Coctail" the best palliative care mixture ever formulated. I even started a thread which I kind of set aside:
Brompton's Cocktail
The problem with the word analgesia is that it conflates nociception with pain. Both are electrochemical events, but pain also has an affective dimension. In pain, an association between sensory data, cognition, emotion and desire has taken place.
I've gotta run, but see if you can get any insight from looking up the central activity of NK-1 antagonists. Said activity sounds a lot like the autonomic effects of opiates and I don't know if any NK-1 antagonist has been developed for the treatment of opiate withdrawal, but I would suspect cocaine's affective role in analgesia depends on a similar mechanism.
Edit: Ignore my second paragraph. It's wrong.Last edited: