Tramadol question

[scottEboy]

could someone who understands pharmacological language please explain the following for me
http://www.rxlist.com/cgi/generic/tramadol_cp.htm
Tramadol is a centrally acting synthetic analgesic compound. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to mc-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mc-opioid receptors.
************************************************
In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in mc-opioid binding.
*********************************************** Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound (see Pharmacokinetics).
Does this mean that increasing the metabolic breakdown of tramadol will increase its opiate effects, thats how it seems to read to me.
Any suggestions on how this would be accomplished if that was the case.
eg - drug interaction
vitamin supplimentation
drawn out slower intake???
Before you ask why bother, tramal is the strongest pain killer my doctor will give me - and I'm one of those lucky ones that reacts quite nicely to it.
Not asking much hey....but some of you out there thrive on answering these kind of questions. Admit it, I know you do.

 

[rollballs]

works like a mild SSRI. There is no drug interaction with the substances you listed.

 

[fairnymph]

Tramadol is a centrally acting synthetic analgesic compound. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to mc-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mc-opioid receptors.
Centrally acting -- means it acts in the brain (as opposed to acting systemically, throughout the body)
synthetic analgesic compound a manmade pain-killing drug
Mechanism : the drug works by binding to various receptors, though the details are much more complicated and numerous. Both the drug itself, and its metabolites (what the body breaks the initial drug down into) can bind to receptors.

In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in mc-opioid binding.
Apparently, the main metabolite of tramadol is much more potent than tramadol itself.

Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests.
Tramadol thus differs enough from other opioids that it does not respond fully to naloxone (what you shoot someone up with when they OD on opiates), unlike other opioids/opiates which DO respond almost completely.

Does this mean that increasing the metabolic breakdown of tramadol will increase its opiate effects, thats how it seems to read to me.
Theoretically, yes, as the M1 metabolite is much more potent that tramadol itself. However, I'm not sure if doing what you suggest is possible, or if it would have desired effect.

Any suggestions on how this would be accomplished if that was the case.
Probably you would want to increase the levels of the enzyme that break down tramadol into the M1 metabolite. Now, that enyzme is CYP2D6, and the only drug I can think of that would induce (increase/speed up) CYP2D6 metabolism would be carbamazepine (an anticonvulsant medication). However, I wonder if perhaps you would get a stronger but SHORTER high as a result?
You raised an interesting question, and I'll have to give it some more thought and do a bit of research to see what else I can come up with.

 

[Ronald]

Wanting to no xactly how much u taken per day. Finden 200mg in the morning good amount ime release throughout the day. started on 50 then 100

 

[gasbo]

As correctly outlined above - it has 2 separate mechanisms of action
(i) opioid (mu-1)
(ii) inhibitis noradrenaline & serotonin reuptake.
That is to say - that the combination of these 2 effects is much greater than either effect added together - ie. a multiplicative effect. The inhibition of noradrenaline and serotonin occurs particularly in the decending pathways for inhibition of pain - in the brain stem and spinal cord.
AS for tampering with CYP2D6 (otherwise known as sparteine oxygenase):
Known inducers are pregnancy, dexamthasone?, rifampicin? (According to my literature sources, carbamazepine has no effect on CYP2D6 - but am happy to stand corrected with a scientific reference).
CYP2D6 inhibitors amiodaroune, celecoxib, chlorpheniramine, cimetidine clomipramine, cocaine, doxorubicin?, halofantrine, reduced-haloperidol, lignocaine, levomepromazine, methadone, mibefradil, meclobemide, quinidine, ranitidine, ritonavir, SSRIs, terbinafine.
The metabolism of tramadol to M1 (O-desmethyltramadol) is slow in humans, and serum concentrations are no more than 25% of those of tramadol.
In healthy volunters, quinidine, which inhibits the metabolism of tramadol to M1, produced only minor changes in measures of analgesia to experimentally induced, standardised painful stimuli, in spit of reducing the M1 serum concentration by up to 75% compared with placebo controlled subjects.
In Summary:
(i) Synergistic activity: more than if either mechanism is used alone and greater than predictive additive mechanism effects.
(ii) tampering with CYP2D6 has not been shown in any randomised controlled trial to alter the analgesic effects of tramadol - as to whether it alters any other 'psych' effect - is unknown.
Ref:
The clinical use of tramadol hydrochloride: Bamigbade, Langford. Pain Reviews 1998;5:155-182
Variable Cytochromie P450 2D6 Expression and MEtabolism of Codeine and other opioid Prodrugs: Implications for the Australian Anaesthetist. Wilcox, Owen. Anaesth Int Care 2000 28:611-19.

 

[scottEboy]

Thanks Gasbo
nice answer thanks for the post.

 

[Ronald]

hey ratboy
why you tolken tramydoll
'bove question need answer

 

[scottEboy]

For Pain 100mg to 150mg
For recreation 300mg to 400mg
Answer your question kid
[ 28 May 2002: Message edited by: scottEboy ]