Opioid Notes: Difference between revisions
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OPIUM ALKALOIDS Thebaine - 6, 14 dimethoxy version of OM. Stimulant rather than analgesic, high dose causes OD Narceine - Bitter, Crystalline, formerly used as a substituted for Morphine. Noscapine - Acts on Sigma, non painkilling. Used commonly in Antitussives. Uninteresting. Blocks Bradykinine B-2 receptors in Stroke patients.
ALKALOID SALT MIXTURES Pantopon - Preparation of all alkaloids present in opium without plant matter. Injectable and almost as potent as morphine.
MORPHINE FAMILY 6-MDDM - 80x potency of M, faster onset and less body load Azidomorphine - 40x potency of M with high affinity to μ Hydromorphinol - Derivative of M but more potent, with a steeper dose-response curve and a longer half life. Script in Sweden. Methyldesorphin - 15x potency of M. Is found in Krokodil Morphinan-6-one (MR-2096) - OM analogue at roughly 5-7mg dosage. RC. FULL NAME: (N-tetrahydrofurfuryl)noroxymorphone N-Phenethylnormorphine - 8-14x potency of M. RAM-378* - N-Phenethyl analogue of Hydromorphinol. It is probably more potent as a result.
3, 6 MORPHINE DIESTERS Diacetyldihydromorphine - Occasionally used an alternative to diamorphine, of which it is faster acting, longer lasting and has less side effects such as euphoria and addiction. However it is equipotent with morphine. Dipropanoylmorphine - Ester of M used to treat severe pain. Rarely used but considered to be safer and less adictive than M. As such carries less side effects, such as euphoria. Slower acting, longer lasting and slightly more potent than M. Nicomorphine - 2-3x the potency of M and commonly prescribed in German speaking countries
CODEINE-DIONINE FAMILY Heterocodeine - Reverse isomer of codeine. 6x potency of M, while Codeine is a prodrug, HC is a direct agonist. Myrophine* - Morphine + 3-benzyl & 6-myristyl chain and acts as a prodrug to M. Has a slow onset of effects and longer duration but reduced potency. Does NOT produce addiction or dependance regardless of dose. Acetyldihydrocodeine - Used in Germany. Close relative of Thebacon, where only the 6-7 bond is unsaturated. 6-Acetyl derivative of dihydrocodeine. Metas into Dihydromorphine. Higher lipophilicity than codeine. Would probably be more potent and longer lasting. Higher BA than codiene. Sch. 1.
MORPHINONES AND MORPHOLS 14-Cinnamoyloxycodeinone - 100x potency of M, interesting. 14-Methoxymetopon - 500x potency of M, can be up to one million x the potency of M if injected into spine. 14-Phenylpropoxymetopon - 2000+x potency of M, when injected into spine up to 1,000,000x. 14-MOP has ceiling effect on respiratory depression (!!) but 14-PPOP untested 3-Acetyloxymorphone - Acetylated analogue of OM 7-Spiroindanyloxymorphone - odd OM analogue, selective d agonist Acetylmorphone - Acetoxy version of Hydromorphone, has a higher BA as a result. Chloroxymorphamine - Derivative of OM and irreversible full agonist Methyldihydromorphine - Related to heterocodeine not dihydrocodeine. Could be 6-9x potency of morphine and a drug of abuse. Metopon - Methylated Hydromorphone, less potent. Interesting though, could have more euphoria N-Phenethyl-14-ethoxymetopon - 60x potency of M but produces less constipation. d & u agonist. Oxymorphol - 6-hydrogenated OM, coming soon... Pentamorphone - few x stronger than fent. short duration but low respiratory depression. Semorphone - 2x potency of M. Partial u agonist and has a ceiling effect on both analgesia and respiratory depression. Thebacon - Thebaine analogue and fairly uninteresting. 6-8x as potent as codiene per mg. Synthesis is easy, same process as methylazation of hydrocodone to hydromorphone with hydromorphinaol/oxymorphinol and a few others as intermediates.
MORPHIDES - HALOGEN EXTENSION NEED TO BE PRODUCED. Chloromorphide - 10x potency of M, Chlorine group attached to the 3 position. Extension of this into other halogens must be made. Fluromorphide - Fluro group attached to the 3 pos.
HYDRAZONES Oxymorphazone - half potency as OM but higher doses last up to 48hrs - irreversible full μ agonist
HALOGENATED MORPHINE DERIVATIVES 1-Iodomorphine - While an increase in activity had not been noted, research into fluorinated morphine analogues is being conducted. 1-Bromocodeine - 1-Chlorocodeine - 1-Bromo-4-5-epoxy-3,6-dimethoxy-17-methyl-morphin-7-ene
Butorphanol - partial ant.-ag. at μ opioid and competitive antagonist/partial agonist at κ opioid. dysphoria is common at normal dose. Drotebanol - Morphinan derivative synthesised from Thebaine with analgesic effects several times more potent than codeine but weaker than morphine. Moderately addictive but limited physical dependance. Under Metabanyl when available as a script. Dextromethorphan (-) - NMDA antagonist / σ1 & σ2 sigma agonist / a3b4, a4b2, a7 nACH antagonist, (very weak) μ, δ & κ opioid agonist, SERT & NET inhibitor, NADPH Oxidase inhibitor. (Race)Methorphan = racemic Dextrorphan (-) - NMDA antagonist / σ1 & σ2 sigma agonist / a3b4, a4b2, a7 nACH antagonist, L-Type voltage-gated calcium channel (LVGCC) blocker, SRI. Cyclorphan - mixed antagonist-agonist with affinity for κ Levophenacylmorphan - 10x potency of M Levofurethylnormorphanol (Ro4-1539) - potent μ opioid agonist 30-60x potency of Levorphanol. Levomethorphan (+) - NDMA antagonist, σ1 & σ2 sigma agonist, μ, δ & κ opioid agonist. Levorphanol (+) - μ, κ & δ agonist, 4-8x potency of M, long duration, no cross tolerance with morphine Norlevorphanol - Opioid analgesic, uninteresting. Phenomorphan - 10x potency of Levorphanol. └--> N-(2-(2-furyl)ethyl) analogue - 60x Levorphanol └--> N-(2-(2-thienyl)ethyl) analogue - 45x Levorphanol Proxorphan - partial κ agonist, lesser partial μ agonist Ro4-1539 (Furethylnorlevorphanol) - 30-60x the potency of M. One of the more potent u agonists from the Morphans.
(Race)Methorphan: L(eft) (+) Levomethorphan >< Dextromethorphan (-) D(exter) --> l=OPIATE >< d=HALLUCINOGENIC OPIATE └--> Racemic mix of both isomers, embodying their properties.
Morphinan (Racemorphan): l (+) Levorphanol >< Dextrorphan (-) d --> l=OPIATE >< d=HALLUCINOGENIC OPIATE └--> Racemic mix of both isomers, embodying their properties.
(Race)Allorphan: l (+) Levallorphan >< Dextrallorphan (-) d --> l= ANTI-OPIOID >< d=NMDA ANTAGONISTS └--> Racemic mix of both isomers, embodying their properties.
3-Hydroxymorphinan: l (+) Norlevorphanol >< Nordextrorphan (-) d --> l=OPIATE >< d=NOOTROPIC └--> Racemic mix of both isomers, embodying their properties.
Oxilorphan: μ antagonist & weak partial κ agonist Dimemorfan - SIGMAERGIC DRUG Xorphanol - mixed ant.-ag. produces convulsions at highest dose tested. Cyprodime - Selective μ opioid antagonist with no affinity for κ or δ receptors Samidorphan - selective μ antagonist. potential for addiction treatment.
Butinazocine - benzomorphan opioid that was never marketed-----------------\ The Benzomorphans have Carbazocine - benzomorphan opioid that was never marketed \ to be my favourite structures. Etazocine - partial opioid agonist with mixed ant.-ag. effects. low potency \_ The Cubist narcotics. Ethylketocyclozocine - partial opioid agonist with mixed ant.-ag. effects The Picassopiates. Ibazocine - benzomorphan opioid that was never marketed They serve no real function Moxazocine - 10x potency of M, partial/mixed ant.-ag. _ except to look pretty to Tonazocine - partial agonist at μ & δ, no adverse effects on breathing / afficionados such as I. Volazocine - benzomorphan opioid that was never marketed / As do I to afficionados such Fluorophen - radioligand, full μ agonist (6x M) & lower affinity for δ / as they, and they to afficonados Zenazocine - partial agonist at μ & δ-------------------------------------/ such as we, and we are such afficionados. Eptazocine - Japanese κ agonist & μ antagonist Pentazocine - mixed ant.-ag. (-) is the κ agonist side, the (+) displays 10x the affinity for sigma receptors. NO μ agonism Phenazocine - related to ^ but stronger analgesic, 4x potency of M Cyclazocine - mixed ant.-ag. Dezocine - Mixed ant.-ag. with high κ antagonism. Low dose=euphoria (μ) High dose=dysphoria (κ). Wierd structure 8-Carboxamidocyclazocine (8-CAC) - κ & μ agonist, long duration. Bremazocine - κ agonist related to Pentazocine Metazocine - analgesic; mixed ant.-ag. at μ, activity also at κ and sigma Alazocine - σ1 agonist, κ opioid agonist & slight NMDA antagonist
MEPERIDINES 4-Fluoropethidine - In comparison to pethidine, it is 50% less potent as an analgesic but 50% more potent as a DRI. (4-iodo & 3, 4-dichloro only increase these differences) Anileridine - Another banned pethidine analogue, probably abused. Higher analgesia than Meperidine due to n-aminophenyl group and acts withing 15 mins orally, lasting 2-3 hours. Benzethidine - 4-phenylpiperidine analogue of pethidine. Probably somewhat more potent and euphoric. Never scripted. Carperidine - fairly normal opiate but unused in medicine and currently LEGAL (08/06/2013) Furethidine - 4-Phenylpiperidine analogue of pethidine. Probably a lot more potent and abuse prone. Never prescribed. Morpheridine - related to meperidine but 4x the potency and does not cause convulsions Phenoperidine - 20-200x the potency of Pethidine. Less hypnotic and than morphine but more emetic (nausea). This can be cured by Haloperidol. Piminodine - similar dose to M, used in 60's and 70's but was banned. It was probably abused widely.
PRODINES Allylprodine - Prodine analogue 23x potency of M Prosidol - Russian Prodine analogue
KETOBEMIDONES Acetoxyketobemidone - Unschedualed analogue of ketobemidone Bemidone - Analogue of Pethidine but significantly less potent, however it has NMDA antagonism like KetoB. Ketobemidone - μ opioid antagonist & NMDA antagonist. More addictive than M
OTHER Loperamide - Peripheral opioid so it cannot cross BBB. useful anti-Diarrhoea med. When used in conjuction with Quinine or Omerprazole can cross BBB and opioid effects are seen. Picenadol - R isomer (or Levopicenadol) is pure μ agonist while S is antagonist. Racemic is mixed that casues low abuse potential but has low κ activity
OPEN CHAIN OPIOIDS
AMIDONES 4,4-Diphenyl-7-Pyrrolidin-1-ylheptan-3-one - Experimental analoge of Dipipanone and Phenadoxone Dipipadone - Lost Ark of the Covenant. Phenadoxone - methadone analogue, similar dose to M, lasts 1-4 hours Levacetylmethadol - Methadone analogue with u agonism and noncompetitive a3b4 NACh antagonism. Brand name Orlaam, prescribed to those unresponsive to methadone or subutex. Long half life (3 days) and heavier affect. Norpipanone - Was not under international control until case reports of addiction arose. Isomethadone - Previously used in medicine. μ- δ- agonism. S-isomer more potent.
METHADOLS Dimepheptanol - related to methadone, has two isomers which also have two isomers so 6 possible isomers including racemic
MORAMIDES Palfium (Dextomoramide) - 3x potency of M but shorter acting. High BA & fast acting, oral feels like shooting. Low LD50 & inconsistent potency (one day you may need 5mg, next day 3mg)
THIAMBUTENES Thiambutenes - Dimethyl-TAB, Diethyl-TAB, Ethylmethyl-TAB. Used in vetinary medicine in Japan. Banned in virtually all countried due to high abuse potential. Anticholinergic and antihistamine properties!
PHENALKOXAMS Dextropropoxyphene - Low potency opiate not absorbed by CYP2D6. Also is a potent, noncompetitive α3β4 NACh antagonist and a weak SRI. Dimenoxadol - Benzillic Acid derivative related to methadone. Banned due to high abuse potential it seems. Dioxaphetyl butyrate - Banned opioid similar to methadone. Possibly in use or previously in use as a med under the names Amidalgon & Spasmoxal.
AMPROMIDES Diampromide - Banned Analgesic related to Propiram. Similar potency to M. Propiram - Slightly more potent than codeine, 3-6hr duration. mixed μ ant.-ag. favouring agonism. affinity for κ & δ, sigma and nmda. 97% oral BA! Phenampromide
OTHERS IC-26 - Methadone analogue with similar potency but Unscheduled. Lefetamine - Weak opiate on the same scale as codeine but has DRI properties. R-4066 - methadone analogue with 212x the potency but a much shorter duration at 3 hours. 2,5-dimethylpiperazine -
3-Methylfentanyl - 400-6000x potency of M depending on isomer (cis-iso more potent) Alfentanil - 1/4 the potency and 1/3 the duration of fent but 4x quicker onset. The businessman's lunch of opiates. Betahydroxythiofentanyl - one of the more favoured fent. analogues by addicts, implying euphoria. Carfentanil - 100x potency of fent., 10000x the potency of M. Used in spetznaz hostage crisis. 10,000x potency of M. Activity in humans starts at 1μg. Lofentanil - more potent and with a longer duration than carfentanil. Mirfentanil - fent. analogue with strong selevtivity over μ. Lower doses it antagonises effects caused by lesser opioids but at higher doses is resistant to antagonists, suggesting it has non-opioid mechanisms. Ohmefentanyl - 6300x morphine at it's most active isomer. Analogues of this are even stronger with one possessing 30,000x the potency of M. Parofluorofentanyl - 150-200x morphine. Sold breifly in 1980. R-30490 - analogue of carfentanil. Most selective μ agonist of all fentanyl analogues Remifentanil - Potent ultra short acting fent. analogue. Potency from between 20 and 100ug. Used in medicine as an anaesthetic under Ultiva. Sufentanil - ~2x Morphine.
7-PET - 300x potency of M, 3-OH derivative is 2200x potency of M. Unscheduled. Acetorphine - 8700x potency of M BU-48 - Etorphine derivative. Selective δ agonist and produces only convulsions with slight antidepression. Buprenorphin - Subutex Cyprenorphine - Buprenorphine analogue, ant.-ag. effects but with higher affinity towards κ. Dihydroetorphine -1000-12000x potency of M depending on RoA. Less addictive than other opiates and is used in a similar fashion to Subutex in China. Etorphine - 1000-3000x potency of M. μ, κ & δ opioid agonist. weak affinity for ORL1 nociceptin/orphanin FQ receptor.
Bezitramide - Prodrug that hydrolyzises in the GI tract to despropionyl-bezitramide. Pulled from the NL's in 2004 after fatal overdose cases. Piritramide - 0.65-0.75x M but still effect is strong and long lasting. Has a small but dedicated fanclub on the 'street'
Etonitazene - Most potent nitazene at 1000-1500x potency of M. Strange structure, abstract from other opioids, with an indole body. xxxNitazene - Differing potencies depending on substitution on the lower 4-phenyl.
18-Methoxycoronaridine - Ibogaine derivative, selective α3β4 nicotinic antagonist, however no affinity for α4β2, NMDA or seretonin. Retains modest affinity at μ & κ opioid. 7-Hydroxymitragynine - Alkaloid in Kratom. Some 17x potency of M. 30x potency of Mitragynine. Conolidine - Eseroline - Metabolite of the ACh inhibitor physostigmine but potent μ agonist Hodgkinsine - alkaloid found in Psychotria colorata plants. Has antiviral, antibacterial and antifungal properties. Also μ opioid agonist & NMDA antagonist. Ibogaine - Addiction CURE. HT2a agonist, κ opioid agonist, NMDA antagonist Mitragynine - Alkaloid in Kratom. Fairly selective μ agonist but little affinity for δ & κ. Noribogaine - Metabolite of Ibogaine. Potent SRI, κ antagonist, weak μ full agonist Pericine - Voacangine - precursor to Ibogine used by iboga plant. Displays similar effects towards addiction as Ibogaine.
BW373U86 - Selective δ agonist at 15x stronger affinity. Analgesic and anti-depressant properties along with BDNF release. Produces convulsions at high doses and reverses respiratory depression produced by μ agonism. Also protects heart muscle cells from death during oxygen deprivation, a result of heart attacks. DPI-227 - highly selective δ agonist with antidepressant effects but produces fewer convulsions than most other dugs in it's family. DPI-3290 - Potent δ & μ agonist but produces little respiratory depression.
Biphalin - endogenous eptide with high affinity for δ & μ receptors. Potency almost 7x greater than Etorphine and 7000x M. Low side effects; no dependancy caused. Casomorphins - opiates found in Cow's milk. DAMGO - synthetic opiate peptide with high μ selectivity. When administered alongside M for 7 days, M had the same effect at the same dose as the first day. I.e. removes tolerance. Deltorphin - High affinity and selectivity, naturally occuring δ opioid agonist. Dermorphin - South American Tree frog skin. Natural opioid peptide. High potency (30-40x M) and selectivity to μ but may be less likely to cause tolerance and addiction. Dynorphins - endogenous opioid peptides, primarily k agonists. Useful in the analysis of addiction. Leu-enkephalin - Endogeneous opioid petide that acts as a δ & μ agonist with strong selectivity for δ. Met-enkephalin - Opioid Growth Factor (OGF), Endogenous opioid peptide. Primary ligand of the δ receptor along with Leu-enkephalin (high potency and selectivity at δ). Low BA & is metabolised rapidly. Opiorphin - Endogenous opioid isolated from human saliva.
3-HO-TCP - PCP analogue. More glutamergic than the PCP analogue. 3-HO-BCP - substitutes for both cocaine and morphine at ~5mg (made-up) AD-1211 - Structure looks unrelated to /most/ other opioid drugs. Mixed Agonist-antagonist at opioid recepts similar to pentazocine. Little to no developement of tolerance/dependence in animal studies. AH-7921 - Selective μ agonist, with 80% potency of M. distributed as an RC, TRs show that it has very little euphoria, indicating euphoria comes from somewhere else. Perhaps sigma? Other opioids are heavily potentiated by it. Perhaps μ agonism is purely analgesic and high comes from a combination of μ & δ with each multiplying the affect of the other. This indicates ultimate opiate high would be moderately selective δ agonist Azaprocin - ~10x potency of M. Faster onset and short duration of action. Discoved in 1963, never been marketed. The derivative subbed on the phenyl ring with a p-nitro group would be more potent by roughly 2.5. (So 25x potency of M) The open ringed 2,6-Dimethylpiperazine analouges would also be active. BRL-52537 - Highly potent and selective κ agonist. Neuroprotective. Bromadol (BDPC) - 500-10,000x potency of M. Similar to PCP analogues & -HO bonds within them. C-8813 (Thiobromadol) - 591x potency of M. μ agonist & δ antagonist to reduce repiratory depression. Making the drug safer. Ciramadol - Opioid related to PCP, Tramadol & Tapentadol. mixed ant.-ag. for μ, low abuse potential and ceiling on respiratory depression. Enadoline - Highly selective κ agonist. Produces visual distortions, dissociation and of course dysphoria similar to Salvia. Herkinorin - Analogue of Salvinorin A but the complete opposite. 100x higher μ affinity and 50x lower κ affinity. Also; "does not promote the recruitment of β-arrestin-2 to the intracellular domain of the μ-opioid receptor, or induce receptor internalization". This means Herkinorin may not produce tolerance or dependance. HZ-2 - κ-opioid agonist, same potency as morphine, long duration, high oral BA ICI-199,441 - high potency, highly selective κ agonist with analgesic effects Methopholine - Isoquinilone derivative with same efficacy as codeine. Could produces corneal opacity. Analogues are more potent with 4'-nitromethopholine at 20x codeine. MT-45 - 80% of M. mixed ant.-ag. and mild NMDA antagonist Nortilidine - Equipotency of M. Opioid activity is in (1S,2R) iso, NMDA antagonism is in (1R,2S) iso. Also acts as a DRI. O-Desmethyltramadol - metabolite of Tramadol. Considerably more potent than Tramadol. Both (+) & (-) isomers lose SRI function but (-) retains NRI functionality. RC. Salvinorin A - Highly potent κ agonist and even more potent D2 partial agonist. Use in therapy for addiction. Salvinorin B ethoxymethyl ether - semi-synthetic analogue of Salv. A. Longer duration @ ~3hrs, active at 50ug & 3000x (!) selectivity over μ & δ Salvinorin B methoxymethyl ether - Similar to ^^ but less selective. 5x potency as Salvinorin A. Deacetylised from Salvinorin A. SC-17599 - selective μ agonist with little or no affinity for δ & κ. Potency in between pethidine & morphine. RWJ-394674 - potent and selective δ agonist, however once inside body it is dealkylated to its monodesethyl metabolite RWJ-413216 which is a potent μ agonist with less affinity for δ. δ activity counteracts the respiratory depression the μ causes. Only prominent side effect is sedation (and euphoria!) TAN-67 - potent and selective δ1 agonist. Has analgesic properties & releases dopamine in the brain. Neuro & cardiac protective properties. Tapentadol - μ & σ agonist & SNRI. 2x Tram. Tifluradom - Benzo derivative but without GABAa agonism. Instead selective κ agonism. U-50488 - highly selective κ agonist with analgesic effects U-69,593 - Potent and selective κ1 agonist. Produces; antinociception, anti-inflammation, anxiolysis (low doses), respiratory depression & diuresis. Also inhibits periphery oxytocin secretion. Not sure if hallucinogenic. W-15 - 5.4x Morphine. RC. W-18 - 10,000x potency of M, structure abstract from any other drug. These super potent opioids are used in vetenarian practice for tranquilising elephants.
OPIOID ANTAGONISTS AND INVERSE AGONISTS - (selective δ antagonists may reduce physical addiction without causing w/d if attatched to an opioid)
Chloronaltrexamine - Irreversible mixed ant.-ag. at μ opioid. 22x more potent than M Cyprodime - Selective μ opioid antagonist with no affinity for κ or δ receptors Diprenorphine - Strongest opiate antagonist available. 100x potency of Nalorphine. Used to reverse effects of super-potent opioids. Levallorphan - μ opioid antagonist, when used with opiate, it potentiates it and removes addiction potential or induces withdrawal in addicts. Nalbuphine - mixed ant.-ag. as is common with this class, there occurs analgesia with no addictive properties. Naloxazone - Irreversible μ opioid receptor antagonist Naloxonazine - Very Potent Irreversible μ opioid antagonist. dimerizes from Naloxazone under acidic conditions Naltrexone - Competitive antagonist at μ & κ receptors, and to a lesser extent, δ. Modulation of the dopaminergic mesolimbic pathway makes it good for countering alcohol dependance as well as Opiate addiction. Blocks the euphoric effects of opioids and is used in rapid detoxification and attenuation of withdrawal. If opiates are used simultaneously, oD may occur. Samidorphan - selective μ antagonist. potential for addiction treatment. IBNtxA - Naltrexone analogue. It is a u opioid agonist however it is not percieved as rewarding in animals, it also does not produce respiratory depression or constipation.
FE 200665 - Is an all D-Amino acid peptide that acts as a restucted K-opioid receptor agnoist. Was dosed at 0.36mg/kg IV. Was compared to 15mg oxycodone. Slightly less than the potency of hydrocodone. Caused Hyperalgesic response in a skin pinch test. Also known as CR665. SoRI-9409 - mixed μ agonist & δ antagonist. moderate analgesia without development of tolerance. Anti-addictive effects for all dopaminergic drugs. 'Synthetic Conotoxin' - Snail toxin derived painkiller 1000x potency of morphine. Non-addictive
Amiphenazole - treatment for OD. counteracts respiratory depression. If Morphine-N-oxide is taken on this, M's potency will increase. Chitosan - linear polysaccharide that can give Morphine up to 60% BA intranasally. Powdered & the ratio is 1.3g : 6.7g (morpine : chitosan) BIMU-8 - NOOTROPIC NMDA antagonists - Inhibit development of tolerance to morphine Tezampanel - ANXIOLYTIC Ibudilast - NOOTROPIC Nuciferine - Not sure where to start with this one... Structurally related to Apomorphine. Associated with Dopamine Receptor Blockade. Tetrahydropalmatine - ANXIOLYTIC Lofexidine - ANXIOLYTIC d & l Phenylalanine (DLPA) - Increases dopamine and endorphin levels, reducing opiate tolerance and even providing an analgesic effect of it's own.
Proglumide - Acts as a d opioid agonist and non selective CCK antagonist. Enhances analgesia produced by opioids and can prevent or even reverse the development of tolerance Devazepide - No affinity for GABAa, selective CCKa antagonist. Lorglumide - Selective CCKa antagonist for treatment of gastrointestinal problems and some forms of cancer as well as Opioid interacting properties.
NOCICEPTINERGIC DRUGS (ORL-1 ant. & ag.'s)
J-113,397 - Highly selective ORL-1 antagonist. Prevents development of opiate tolerance, stimulates dopamine release, cognitive enhancer SB-612,111 - Selective ORL-1 antagonist but several times the potency of ^^ MCOPPB - Potent, selective ORL-1 agonist with only moderate affinity for μ, even less for δ & κ. Anxiolytic with no inhibition of memory, motor function or sedation NNC 63-0532 - Potent, selective ORL-1 agonist. Ro64-6198 - Potent, selective ORL-1 agonist with 100x selectivity over others. In rats produced anxiolytic but no anticonvulsant effects. Impairs Short term memory & increases appetite. Reduces analgesic effects of M but no preventing tolerance. In primates it showed analgesic behaviour without respiratory depression. Menabitan - potent cannabinoid receptor agonist with anti-nociceptive effects
ENKEPHALIN PROTEASE INHIBITORS
RB-101*** - Inhibits enzymes responsible for breaking down enkephalin (regulates nociceptin). Weak μ & δ affinity and slight σ1. Potentiates opiates, stops withdrawal symptoms, no addiction potential, produces no respiratory depression. Also exerts very potent antidepressant and anxiolytic effects. Not orally active so analogues vv were developed. RB-120 - Orally active version of ^^. This is best atm. RB-3007 - Another Enkeph. PI & Nociceptin antagonist