1. Dear Drugs-Forum readers: We are a small non-profit that runs one of the most read drug information & addiction help websites in the world. We serve over 4 million readers per month, and have costs like all popular websites: servers, hosting, licenses and software. To protect our independence we do not run ads. We take no government funds. We run on donations which average $25. If everyone reading this would donate $5 then this fund raiser would be done in an hour. If Drugs-Forum is useful to you, take one minute to keep it online another year by donating whatever you can today. Donations are currently not sufficient to pay our bills and keep the site up. Your help is most welcome. Thank you.
    PLEASE HELP
    Dismiss Notice

Ah-7921

Discussion in 'Pharmacology' started by Piglet, Nov 23, 2010.

  1. Piglet

    Piglet Titanium Member

    Age:
    46
    Reputation Points:
    673
    Joined:
    May 28, 2005
    Messages:
    1,272
    Anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides

    This is a brief article on the totally synthetic, totally unrelated to any controlled compound, opioid analgesic AH-7921. Both the 3,4 dichloro & the N,N dimethyl are needed to produce a potent analgesic...


    British journal of pharmacology 49 (1): 158P–159P

    R. T. BRITrAIN, D. N. KELLETT, M. L. NEAT & R. STABLES

    Department of Pharmacology, Allen & Hanburys Limited, Ware and Huntingdon Research Centre, Huntingdon.

    In the mouse, certain N-substituted cyclohexylmethylbenzamides markedly inhibited writhing induced by phenylquinone and the nociceptive responses to being placed on a hot plate (Table 1). The results indicated that these compounds possessed analgesic activity and [3,4-dichloro-N-fl-(dimethylamino)cyclohexyl] methylbenzamide (AH 7921) was selected for detailed study in higher species.
    In the conscious dog the minimal oral effective doses of AH 7921, morphine and codeine required to completely suppress the pain response to electrical stimulation of the dental pulp (Neat & Peacock, 1971) were 1.25±0.8, 1.25±0-3 and 3.5±0±6 mg/kg respectively. In a similar test using the conscious rhesus monkey the minimal antinociceptive doses of AH 7921, morphine and codeine were 13.8±1-2, <5.0 and 11.3±0.8 mg/kg espectively. Anti-nociceptive doses of AH 7921 caused no overt behavioural effects in the mouse, dog or monkey but higher doses (50 mg/kg orally) caused slight central nervous system depression. The addictive liability of AH 7921 was next investigated. AH 7921 was administered orally to rats, 5 mg/kg 3 times a day increasing to 20 mg/kg 3 times a day over 5 days. On the fifth day the animals were challenged with naloxone 0.25 mg/kg s.c., which caused an abstinence syndrome similar to that produced in animals that had received morphine on a similar dosage schedule. In the rhesus monkey single doses of AH 7921, 5-10 mg/kg s.c., completely alleviated the abstinence syndrome in morphine-dependent animals. In addition, AH 7921, 7-5 mg/kg s.c. twice daily, increasing to 30 mg/kg s.c. twice daily over 30 days, produced physical dependence in naive monkeys which was demonstrated in two ways. Nalorphine, 2 mg/kg s.c., induced an abstinence syndrome typical of that seen following morphine withdrawal in morphine-dependent monkeys. Secondly, on terminating AH 7921 treatment abstinence signs appeared over a period of 24-48 h. AH 7921 would be classed as a narcotic analgesic having high addictive liability. These findings are relevant to the relationship between structures of morphine-like compounds and addictive liability.

    TABLE 1. Anti-nociceptive effects of some N-substituted cyclohexylmethylbenzamides in the mouse

    R1-CONH.CH2 R2
    Phenylquinone test Hot plate test
    AH no. R, R2 ED50 mg/kg orally ED50 mg/kg s.c.
    7563 -N(CH,)2 15-3 (7-6-31-0) 15-5 (5-4-42-0)
    8533 2Cl -N(CH,)2 >100 60
    8532 3Cl -N(CHS)2 16-0(8-4-34-0) 95 (4-3-24-5)

    8529 4Cl -N(CH,)2 7-3(3-3-16-1) 50(1-7-15)
    7921 3,4Cl -N(CHS)2 0-85 (0-4-1*7) 2-5 (1-2-6-4)

    7959 3,4Cl piperidine >100 > 100
    8507 3,4Cl N-methyl piperizine >100 >100

    Morphine 11 (0-7-1-8) 2-8(1-1-48)
    Codeine 5 8 (2-9-11-6) 17-0(9-1-32-0)

    We would like to thank Dr. G. B. A. Veitch, University of Aston, Birmingham and the Research Chemists of the External Projects Unit, Allen & Hanburys Ltd., Ware for the synthesis of the compounds used in this work.

    REFERENCE
    NEAT, M. L. & PEACOCK, R. (1971). Implantation of electrodes in the dentine of an upper canine tooth in the dog. Br. J. Pharmac., 43, 476-477P.
     
    Last edited: Nov 23, 2010
  2. Piglet

    Piglet Titanium Member

    Age:
    46
    Reputation Points:
    673
    Joined:
    May 28, 2005
    Messages:
    1,272
    SWIM should point out that this stuff can be synthesised in a single step from commercially available & non-suspicious chemicals... and it's equipotent with morphine.
     
  3. NeuroChi

    NeuroChi is not his mind Staff Member

    Reputation Points:
    4,886
    Joined:
    Dec 18, 2007
    Messages:
    4,961
    How does its lipid solubility compare?
     
  4. Valseedian

    Valseedian Silver Member

    Reputation Points:
    318
    Joined:
    Apr 30, 2009
    Messages:
    373
    care to share the tek? Ive UTFSE with no luck...
    swim is very interested.
     
  5. sam o

    sam o Newbie

    Reputation Points:
    -28
    Joined:
    Jan 20, 2006
    Messages:
    20
    Very interesting chemical, I'v done research with analgesic peptides mainly ones that pass the BBB , in hope to find a stable one with a long duration.
    Dermorphin seems to fit the bill:cool:

    If AH-7921 is on parr with morphine would the starting dosage and duration be basically the same?

    Anyone want to take a guess with AH-7921 , passing all drug screenings(GS/MS) ?

    Thanks.
     
  6. Piglet

    Piglet Titanium Member

    Age:
    46
    Reputation Points:
    673
    Joined:
    May 28, 2005
    Messages:
    1,272
    Will it pass blood-screenings? - YES!

    Lipid solubility? - partition coefficient unreported but onset/duration similar to morphine & very active orally. The Ki isn't actually that great but the compound is 'highly lipophilic' so the concentration in the brain will be high compared with M.

    Addictive Liability? - Low (Straub Index)

    Synthesis? - It's an amide: Find the appropriate acid chloride & (di)amine: they ARE out there & easy to find (SWIM took 60 seconds). Schotten–Baumann type synthesis was used by Dr. G. B. A. Veitch. Sadly the good doctor is no longer with us so SWIM cannot ask for details!
     
    Last edited: Nov 25, 2010
  7. sam o

    sam o Newbie

    Reputation Points:
    -28
    Joined:
    Jan 20, 2006
    Messages:
    20
    What would be a good starting dosage based on the abstract listed above(orally and i.v.)
    Do you think most of the studies were done using AH-7921 in it's hydrochloride form? (I see that wikipedia also has info. on it's hcl form)

    Thanks
     
  8. Jasim

    Jasim Gold Member

    Reputation Points:
    2,795
    Joined:
    Nov 13, 2008
    Messages:
    1,922
    I just want to point out that the comment regarding dosage is NOT a valid assertion with any substance. Dosage and efficacy are two completely different concepts in pharmacology. A drug can have an identical efficacy, but vary dramatically in the dosage require to meet that effect. This would be a variance in potency.

    Regardless, with any research chemical without good documentation on human dosages one should take extreme caution and increase dose slowly with a starting dose well below the expected threshold for any noticeable effect.
     
  9. sam o

    sam o Newbie

    Reputation Points:
    -28
    Joined:
    Jan 20, 2006
    Messages:
    20

    I understand your concerns ,but I have NO intention on trying this chemical, just a hypothetical thats all.

    I appreciate your post thou.:)
     
  10. DynoMiTe

    DynoMiTe Silver Member

    Reputation Points:
    9
    Joined:
    Mar 1, 2009
    Messages:
    73
    Any more info on this? My Buddha statue has been looking into a custom synthesis of this but I do not want to jump in with out knowing more about it.
     
  11. DynoMiTe

    DynoMiTe Silver Member

    Reputation Points:
    9
    Joined:
    Mar 1, 2009
    Messages:
    73
    I know SWIM was the last one to post. SWIM will have this tomorrow. It is getting sent straight away to a lab to get testing with GC/MS and HPLC. SWIM will post the results ASAP.
     
  12. xJSL

    xJSL Silver Member

    Reputation Points:
    249
    Joined:
    Mar 3, 2010
    Messages:
    282
    Just wondering, why would the addiction liability of a drug like this be low? I mean, any drug that can bind to the mu opioid receptor with a similar potency as morphine is bound to be pretty addictive.
     
  13. Alfa

    Alfa Productive Insomniac Staff Member

    Age:
    116
    Reputation Points:
    12,274
    Joined:
    Jan 14, 2003
    Messages:
    30,152
    Gender:
    Male
    Location:
    The Netherlands
    AH-7921 seems to be going around now. More information would be welcome.
     
  14. Lady Codone

    Lady Codone Titanium Member

    Reputation Points:
    890
    Joined:
    Jan 23, 2009
    Messages:
    905
    SWIM will likely be trying some of this soon and would appreciate any/all advice she can get. Is the high more similar to opium/hydrocodone (heavy, sedating) or oxycodone (stimulating/energetic)? How is it on side effects like nausea and dizziness? What's a relatively safe starting dose for an opiate-naive researcher?

    From reading, it appears that sublingual is the best ROA...right?

    So much to learn! ;)
     
  15. Baba Blacksheep

    Baba Blacksheep Titanium Member

    Reputation Points:
    431
    Joined:
    May 29, 2011
    Messages:
    413
    Moved to Experiences.
     
    Last edited: Aug 26, 2012
  16. Rob Cypher

    Rob Cypher

    Reputation Points:
    2,465
    Joined:
    May 30, 2010
    Messages:
    2,332
    None of the reports I've read on DF or other forums have been very positive about this substance - it appears less effective than tramadol unless you go into the 200-500 mg range, and then there's a chance of sudden OD around that range (especially when mixed with other things, as some are want to do). I'd avoid just based on word of mouth alone.
     
  17. chupamivergaguey

    chupamivergaguey Silver Member

    Reputation Points:
    225
    Joined:
    Jan 10, 2009
    Messages:
    320
    Just had some blood work ordered after ~5 months at 30-120mg/day. This should be interesting, and I'll report back once I hear something.
     
  18. chupamivergaguey

    chupamivergaguey Silver Member

    Reputation Points:
    225
    Joined:
    Jan 10, 2009
    Messages:
    320
    Read the tea leaves:

    LIPID PANEL
    [FONT=&quot]CHOLESTEROL(<200): 185[/FONT]
    [FONT=&quot]TRIGLYCERIDES(<150): 254[/FONT]
    [FONT=&quot]HDL CHOLESTEROL(>39):44[/FONT]
    [FONT=&quot]CALCULATED LDL CHOL(<100):90[/FONT]
    [FONT=&quot]RISK RATIO LDL/HDL(<3.55): 2.05[/FONT]
    [FONT=&quot]
    [/FONT]
    [FONT=&quot]2834 TSH REFLEX TO FREE T4[/FONT]
    [FONT=&quot]TSH REFLEX TO FREE T4(0.5-4.7): 1.4[/FONT]
    [FONT=&quot]
    [/FONT]
    [FONT=&quot]1000 CBC (COMPLETE BLOOD COUNT)[/FONT]
    [FONT=&quot]EOSINOPHILS(0-7): 2[/FONT]
    [FONT=&quot]WBC(4.0-11.0): 8.8[/FONT]
    [FONT=&quot]MONOCYTES(4-13): 10[/FONT]
    [FONT=&quot]PLATELET COUNT(130-400): 220[/FONT]
    [FONT=&quot]RBC(4.10-5.70): 4.95[/FONT]
    [FONT=&quot]BASOPHILS(0-2): 1[/FONT]
    [FONT=&quot]HEMOGLOBIN(13.0-17.0): 15.3[/FONT]
    [FONT=&quot]LYMPHOCYTES(19-48): 30[/FONT]
    [FONT=&quot]RDW(11.0-15.0) 14.2[/FONT]
    [FONT=&quot]NEUTROPHILS(40-74): 57[/FONT]
    [FONT=&quot]HEMATOCRIT(37.0-49.0): 45.2[/FONT]
    [FONT=&quot]MCV(80.0-100.0): 91[/FONT]
    [FONT=&quot]MCH(27.0-34.0): 30.8[/FONT]
    [FONT=&quot]MCHC(32.0-35.5): 33.8[/FONT]
    [FONT=&quot]
    [/FONT]
    [FONT=&quot]BASIC METABOLIC PROFILE[/FONT]
    [FONT=&quot]GLUCOSE(65-100): 78[/FONT]
    [FONT=&quot]BUN(8-25): 13[/FONT]
    [FONT=&quot]CARBON DIOXIDE(22-32): 33[/FONT]
    [FONT=&quot]CALCIUM(8.5-10.5): 10.3[/FONT]
    [FONT=&quot]POTASSIUM(3.5-5.3) 4.2[/FONT]
    [FONT=&quot]CHLORIDE(96-108): 98[/FONT]
    [FONT=&quot]SODIUM(133-145): 140[/FONT]
    [FONT=&quot]CREATININE(0.8-1.4): 0.9[/FONT]
    [FONT=&quot]eGFR AFRICAN AMER.(>60): 114[/FONT]