apo-morphine:
It's "potency" is to make you vomit. Period. You gonna vomit like hell. In very low doses or combination with metoclopramid, it can be used to help with opioid withdrawal.
It exhibits (in vitro) high binding affinity to D4-receptors, moderate affinity to D2-, D3- and D5-receptors and low affinity to D1-receptors. Additionally, it shows moderate affinity for adrenergic 1D, 2B and 2C-receptors, and for 5HT1A, 2A, 2B and 2C-receptors subtypes.
Apart from the plain affinities, the main
relevant activities are as full D1-agonist and partial D1-agonist.
Metabolism includes mainly oxidation, N-demethylation and metabolism by COMT, glucuronidation and sulfation. Only 0.3 % is excreted unchanged, but there are no known, significantly active metabolites.
Refs:
- Neurology 2004, 62, S8-S11
- J Pharmacol Exp Therap 2002, 303, p.805
- Clin Neurpharmacol 1998, 21, p.159
Apo-codeine:
Pharmacological action of apocodeine is very similar to apomorphine's but significantly weaker. It's mainly emetic, in lower doses helpful with erectile dysfunction. The same counts for the metabolism. No relevant metabolites known.
When coadministered with apomorphine, it antagonizes the dopaminergic effects of the former in several behavioral tests and on the striatal adenylate cyclase (showed with intact mice).
Refs:
- Patent WO 2000069416 (2000)
- Neuropharmacology 1979, 18, p.165
- Exp Neurol 1977, 55(1), p.56
Morphine: No comment, as this one is covered in numerous publications online, as well as in diverse threads here.
Codeine:
No comment, as this one is covered in numerous publications online, as well as in diverse threads here.
Codamine:
The only relevant biological activity that I found was some action against Plasmodium falciparum (the parasite that causes malaria tropica). The compound is hardly studied, no infos about metabolism or any relevant actions in humans.
Codamine itself is a metabolite of laudanosine.
Refs:
- J Nat Prod 2007, 70(9), p.1536
- Drug Metab Dispos 1986, 14(6), p.703
Thebaine:
Thebaine doesn't show any relevant analgesic effects and, as was shown, has therefore no relevant mu-receptor binding (around 1000x less than morphine). At higher doses, it's main action consists of causing strong colvulsion, leading finally to death. The structure is sometimes compared with strychnine, which is also taken to explain its convulsive action. Naltrindole failed to prevent the letal convulsions induced by thebaine, suggesting that delta-opioid-interaction is not relevant, too. The naturally occuring isomer showed a Ki at delta-receptors of 1.02 muM. But affinity is not always activity! Finally, it was shown that thebaine possesses a quite high affinity for glycine-receptors (displacement of [3H]-strychnine with an IC50=1.0 muM), thus confirming the aforementioned convulsive action.
Main metabolites were shown to be morphine, codeine and oripavine and nororipavine, as well as northebaine. Oripavine is the major metabolite, morphine and codeine appear only in minute quantities, which do not contribute significantly to the biological activity of the compound. Interestingly, the proposed metabolism pathways are the same as the biosynthetic pathways in poppy.
Refs:
- Life Sci 1991, 48, p.2165
- Eur J Pharmacol 1999, 378, p.323
- PNAS USA 1988, 85(4), p.1267
- Eur J Pharmacol 1999, 365(2/3), p.143
- Gen Pharmacol 1981, 12, p.477
Oripavine:
The pharmacological action is somewhere in-between morphine and thebaine, as this compound shows analgesic properties comparable with morphine but, as well, induces clonic-tonic, potentially letal convulsions.
Metabolism of oripavine is hardly studied. Very most publications deal with derivatization to more "useful" opioids.
Laudanosine & Laudamine:
Correct spelling of "laudamine" is "laudaNine"!
Metabolism of laudanosine was studied in dogs and rabbits, main metabolites were shown to be the following:
pseudocodamine (4'-desmethyllaudanosine)
pseudolaudanine (6-desmethyllaudanosine)
laudanine (3'-desmethyllaudanosine)
codamine (7-desmethyllaudanosine)
N-norlaudanosine
N-norpseudocodamine
N-norpseudolaudanine
Laudanoisne itself is a metabolite of atracurium and cisatracurium.
Laudanosine showed some weak action at SK-channels (=Ca2+-dependent K+-channels), IC50=40 muM. It also crosses the blood-brain barrier and may cause excitement and seizure activity. Additionally, activity at GABA-, opioid- (which?), and nAcCh-receptors were shown, although I can not help out here with definite values. At nAcCh-receptors, laudanosine acts as inhibitor, especially at the brains alpha4beta2-receptor in the muM range, as well as the ganglionic alpha3beta4, alpha3beta4alpha5 and homomeric alpha7-subtypes.
Refs:
- Drug Metab Dispos 1986, 14(6), p.703
- Eur J Anaesthesiol 2002, 19(7), p.466
- Anaesthesiology 2001, 94(4), p.643
Laudanidine & Palaudine & Papaveraldine:
No useful info found, sorry. Actually, there are publications available but these do not deal with your requested topics.
Papaverine:
Useful info about the biological action in men can be found at Wiki:
http://en.wikipedia.org/wiki/Papaverine
Metabolites consist mainly of the first demethylated, then glucuronidated and sulfated (spelling?) conjugates, none of them with biological activity worth mentioning IMO. Positions 4' and 6 are the ones that get mainly metabolized, but the others are also transformed in such a fashion.
Refs:
- J Pharm Pharmacol 1982, 34(4), p.264
- Quant Mass Spectrom Life Sci, 1st Proc Int Symp, 1977, Meeting Date 1976, p.133-43
Phenyldihydrothebaine:
I just found chemically related papers (synthesis and derivatization), so no topics for Bluelight. No info about metabolism, active metabolites or alike.
Neopine:
Also known as "beta-codeine", as it is an isomer of codeine.
Practically all studies involving neopine deal with chromatographic methods. Noone seemed to be interested in metabolic issues. The only thing I found, was that it could be used as chromatographical marker for codeine-abuse, because it appears in the urine of such (ab)users. It can also be used to distinguish between codeine- and heroine-abuse. The mentioned transformation is explained by double-bond migration in the C-rinf from pos. 7-8 to 8-14
Refs:
- Anal Bioanal Chem 2005, 382(3), p.830.
Noscapine (narcotine):
The main metabolites are 6,7-dihydroxynoscapine and its desmethyl product at either position 6' or 7', resp.
The action of noscapine itself is mainly antitussive. Some works suggest that this actions is mediated through bradykinin receptors in the airways. The antitussive effect of noscapine is not mediated via the mu, kappa or delta opioid receptors, as naloxon failed to reverse the observed action.
Refs:
- Acta Physiologica Hungarica 2003, 90(2), p.147
- Eur J Pharmacol 1988, 145(2), p.195-203
- Mol Pharmacol 1992, 42(4), p.619
Sanguinarine:
The main metabolite seems to be dihydrosanguinarine.
I can't server with a concrete mechanism, but sanguinarine's main action consists of blowing up cells. GEE!! It's a nice apoptosis inducer. Nothing to deal with. I would estimate that the metabolites show similar actions. It is also known to cause DNA damage and p53-independent cell death. Watta small mo'fucker!
One interesting sidenote: In my country,
Chelidonium majus (
http://de.wikipedia.org/w/index.php?title=Bild:Schoellkraut01.jpg&filetimestamp=20060430220648), a plant containing significant amounts of sanguinarine, is used in folk-medicine
topically against warts. The plant's juice (nicely orange coloured due the sanguinarine and related alkaloids) is dipped onto a wart, 2-3 times a week and cures the wart within around 2 weeks. It worked for me and relatives more than dozen times. This tells a bit about the cytotoxic properties of such alkaloids.
Refs:
- Food Chem Toxicol 2008, 46(7), p.2546
- J Cell Biochem 2008, 104(3), p.895
- Chemico-Biol Interact 2008, 172(1), p.63
YO!!! Murphy
