Project Narco: Drug Addiction: Some Facts, Some Data

Project Narco: Drug Addiction: Some Facts, Some Data: Some data on addiction and substance use seems to fly in the face of our popular understanding...

Obscure Opioids Appearing as RC's

MT-45

Also known as IC-6.

MT-45 is a synthetic opioid analgesic discovered in the 1970's. Its mu agonist properties are evident although it may possess mixed agonist/antagonist properties similar to other compounds in its chemical class. It has a potency of roughly 3/4ths that of morphine. 

MT-45 is a N,N-di-substituted piperazine derivative. It structurally unrelated to most other opioids, with the exception of lefetamine, an atypical opioid with stimulant properties.

Little anecdotal information exists on the subjective effects of MT-45 (not to mention its toxicity profile or excretion patterns), however users have reported morphine-like effects ranging from mild to overbearing which last a few hours. Most users seem to administer MT-45 by the oral route.

AH-7921

Also known by the unofficial name Doxylam.

AH-7921 is a synthetic opioid selective for the morphine (micro, mu) receptor. It has a potency of roughly 3/4ths that of morphine. It is structurally unrelated to most other opioids and has not been used clinically, but has rarely appeared as recreational drug or research chemical.

Most users describe moderate analgesia with little euphoria. AH-7921 can be expected to have effects comparable to pentazocine, butorphanol, and other partial opioid agonists.

Pyrovalerone Derivatives: A Driving Force in the RC Market

Background Info:

In 1967, a series of N-pyrrolidino ketone compounds were patented. The primary compound of this series was 1-(methylphenyl)-2-(pyrrolidinyl)-pentanone, now more popularly known as pyrovalerone. Synonyms for pyrovalerone are Centroton, Thymergix, Valerophenone, O-2371, and of course PV.

The Parent Compound:

Out of all the known/patented pyrovalerone analogues, only the parent compound has been widely studied.

Studies of pyrovalerone form the basis of our understanding of its structural analogues. PV is listed in the US as a Schedule 5 Controlled Substance, and has been used in the clinical setting as an anorectic and wakefulness promoting agent. 

Pyrovalerone (and by extension, its derivatives) is a structural relative of the CNS stimulant cathinone, and can therefore be referred to as a substituted cathinone.

There are 2 key characteristics of pyrovalerones distinguishing them from immediate cathinone derivatives; 1) a tertiary amine rather than a primary or secondary amine, which is incorporated into a heterocyclic five membered, pyrrolidine ring system (4 carbon and 1 nitrogen). And 2) an extended five carbon backbone (affording a pentiophenone structure as opposed to a propiophenone).

In the 1960's Stille and Holliday confirmed stimulant activity of PV in animals. In 1971 it was shown to reduce chronic fatigue in humans. Later it was shown to inhibit NE reuptake and induce NE release in rat heart. A study in the 1990's observed the parallel between its locomotor stimulant activity and its dopamine transporter occupancy in mice. Note; NE = norepinephrine, DA = dopamine.

In 1969, the methylenedioxyphenyl analogue of pyrovalerone, now well known by the abbreviation MDPV, was patented by a pharmaceutical company known by Boehringer Ingelheim. MDPV was never marketed and remained an obscure stimulant until recently appearing as a popular designer drug.

In summary, PV, along with many analogues thereof, are known ligands for the monoamine transporters; with a preference for NET and DAT, and for the most part, negligible interaction with SERT systems. As a general rule, compounds of this class can be presumed to act as powerful CNS and cardiovascular stimulants.

Appearance of Obscure PV Analogues:

MDPV

In the mid-2000's, MDPV (mentioned in section 1 paragraph 5) appeared on the pseudo-legal market as a designer drug, being sold by names such as Cloud 9 and Supercoke. It was also the main constituent in the first generation of novelty "bath salts". Reading news reports from the time of peak popularity for these items, it becomes apparent that the one defining commonality amongst the walking-dead style anti-drug propaganda is the description of a paranoid/agitated state resembling the symptoms of amphetamine-psychosis. It's fair to say that most bath salt users who exhibited these bizarre, stereotypic behaviors were experiencing symptoms of amphetamine psychosis, caused in many cases by the MDPV in the bath salts they were consuming.

MDPV is simply an analogue of PV containing oxygen atoms at carbons 3 and 4 of the benzene ring, bound by a methylene bridge. MDPV, like pyrovalerone, is an NDRI, and in its pure form is a powerful CNS and cardiovascular stimulant. Based on anecdotal reports it is a potent reinforcer, and it also seems to be, relative to other sympathomimetic amines, particularly prone to inducing psychotomimetic symptoms (as is evident by the many stories, albeit dramatized, of bath-salt psychosis).

MDPV is still being synthesized by Chinese labs (China seems to be the main manufacturer and exporter of RC's), but has been rarely encountered in the US since late 2011, when it was classified as a Schedule 1 Controlled Substance, along with a number of other substituted cathinones (namely mephedrone and methylone).

MDPV carried a devoted legion of followers, (specifically heavier stimulant users who prefer the convenience of licit substances), and the 2011 federal ban left a major demand to be filled. Since this time, new PV analogues have appeared periodically, usually touted by the manufacturers as MDPV replacements (although the deepest of MDPV devotees tend to rate each subsequent PV compound as inferior to MDPV).

A-PVP

APVP was mentioned in the 1967 patent for pyrovalerone. It can be described chemically as 1-phenyl-2-

(pyrrolidinyl)-pentanone. Synonyms include O-2387, a-PVP, O-desmethylpyrovalerone, or APVP, or PVP.  No substantial body of research exists on the properties of a-PVP, although its metabolism and excretion patterns in rat urine have been documented. It is presumed to act as a CNS and cardiovascular stimulant.

APVP is simply the O-demethylation product of pyrovalerone. It appeared in the early 2010's and became a popular grey-market product following bans on MDPV. Its effects are reported to be more or less comparable to MDPV. It has seemed to remain the gold standard in terms of MDPV replacements.

Based on reports by users, APVP in its pure form produces powerful CNS/cardiovascular stimulation. Its effects are apparent in doses under 10mg.

A-PVT

A-PVT is an analogue of A-PVP where the benzene ring has been replaced with a thiophene ring. It can be referred to chemically as 1-(thiophenyl)-2-(pyrrolidinyl)-pentanone. Little to no research exists on the properties of A-PVT. 

The exchange of the phenyl ring for a thiophenyl ring in a PV compound was first documented by Lancelot, and was reported to result in compounds of similar potency as both dopamine and norepineprine reuptake inhibitors.

APVT has very recently appeared as an RC. While many US RC merchants have become reluctant to offer APVP (or substituted cathinones in general), APVT has been promoted as a viable alternative. Users have reported mild effects similar to APVP.

MPHP
\
MPHP is a homologue of pyrovalerone, with the only difference being the addition of an extra carbon (or
rather CH3 group) on the alkyl side chain, affording a 6 carbon hexane backbone. It can be referred to chemically as 1-(4-methylphenyl)-2-(pyrrolidinyl)-hexanone.

MPHP has been encountered in recent years as a designer drug, and is speculated to be the chemical dubbed by chinese labs as "PV4", derived from a new naming scheme for pyrovalerone analogues marketed as MDPV replacements.

The general SAR pattern in the pyrovalerone series seems to be 'greater activity with a longer alkyl backbone', with the maximum chain length being seven carbons. The most potent compounds known in this series consist of a five (pentyl) or six (hexyl) carbon backbone.

Side note; MPHP is technically not a true "pyro-valerone", as it contains a lengthened chain, however it should still fall under the category of pyrollinyl ketones.

PV8

There has been a new RC appearing in recent weeks being referred to by manufacturers as "PV8".
Manufacturers claim it is the "best" MDPV replacement yet. Nothing is known about this compound, and only speculation (although from a semi-reputable source) exists as to what the chemical name actually is for PV8. The supposed chemical name is 1-phenyl-2-(butylamino)-heptanone. If this is indeed the correct chemical then it contains an unusually long alkyl backbone (although still conforms to the rule of 7 carbons or less) and contains neither a tertiary amine nor a heterocyclic pyrrolidine ring.

Naphyrone 

Naphyrone is a unique analogue of pyrovalerone. It appeared on the grey market as a replacement for mephedrone, a cathinone derived stimulant and entactogen. It can be referred to chemically as 1-napthylenyl-2-(pyrrolidinyl)-pentanone. Synonyms for naphyrone include O-2482 and napthylpyrovalerone. It was reported to be the ingredient behind a product sold as NRG-1, but later analyses confirmed that only a portion of NRG-1 samples actually contained naphyrone.

Naphyrone differs from pyrovalerone with the fusion of an additional benzene ring to carbons 3 and 4 of pyrovalerone's benzene ring, forming a napthyl feature.

Naphyrone is pharmacologically distinct from other pyrovalerones in that it shows significant affinity to all three monoamine transporters; it acts as a triple reuptake inhibitor, meaning that it inhibits the uptake of norepinephrine, dopamine, and serotonin. This was the only PV compound to show activity in nanomolar (nM) concentrations.

Naphyrone is a schedule 1 controlled substance in the United States.

Further Reading:

EMCDDA Synthetic Cathinones Profile

Pyrovalerone Analogues: A Promising Class of Monoamine Uptake Inhibitors

A Forensic Toxicologist's Review of Pyrovalerone Analogues and a Review of Federal CSA Legislation

DrugsForum - APVP Drug Info Page

Monoaminergics: Household Names

Common CNS stimulants and their modes of action clarified. I'll probably make additions to this list over time.

NDRI: This is an abbreviation for Norepinephrine and Dopamine Reuptake Inhibitor. NDRI's work by inhibiting the function of the dopamine and norepinephrine transporters, usually causing a subsequent increase in available synaptic dopamine and norepinephrine.

NDRA: This is an abbreviation for Norepinephrine and Dopamine Releasing Agent. NDRA's work by inhibiting the function of the dopamine and norepinephrine transporters while reversing their flow (through a process known as phosphorylation), causing the release of dopamine and norepinephrine into synaptic vescicles.

Dopamine Transporter (Source: Wikipedia)

amphetamine - NDRA, NDRI
methamphetamine - NDRA, NDRI
cathinone - NDRA, NDRI
methcathinone - NDRA, NDRI
napthylaminopropane - Triple-RA/RI, serotonergic agonist/partial agonist
cocaine - SNDRI
methylphenidate - NDRI
APVP - NDRI
Naphyrone - SNDRI
prolintane - NDRI
pipradol - NDRI
bupropion - NDRI
6-APB - Triple-RA/RI, 5HT agonist
5-APB - Triple-RA/RI, 5HT agonist
MDMA - Triple-RA/RI
MDA - Triple-RA/RI, 5HT2A agonist
4-MEC - Triple-RA/RI
4-FA - Triple-RA/RI
2-FMA - NDRA, NDRI

Observations With 4-MEC, 4-FA, and 2-FMA

Based on what I've heard reported first hand and throughout the web, I've noted the following consistencies, in hopes of providing a better general understanding of each of these compounds.

2-FMA 

2-FMA seems to be very active in doses of 50 mg and up.

Provides a clean, mellow, stimulated state for a few hours

It causes a heavy, shortlived cough and a strange tickling sensation in the urinary tract when taken by more direct routes, as does its 4-desfluoro parent (methamphetamine).

Powder is clean white with a snowy appearance. Powder seems to dissolve readily and easily in water.

Reports on 2FMA being a "functional" stimulant seem to be on the mark. This seems to be a compound that the well-disciplined researcher could function adequately on during work or while performing other important duties.

4-FA 

4-FA seems to be very active in doses of 50mg and up. Oral dosing may require slightly larger amounts (I'll estimate 75mg or more). 

Product appeared as a fine snow-like powder; its color was white but compared to 2-FMA it could be considered a slight off-white.

Produces effects similar to both 2FMA and 4MEC. 

It has mild but noticeable empathogen qualities.

It produces significant mydriasis (pupil dilation), like ecstasy and 4MEC.

It causes a heavy, shortlived cough and a strange tickling sensation in the urinary tract when taken by more direct routes, as do methamphetamine and 2-FMA. Nausea is common especially with higher doses. It may be a good idea to stay near the toilet when first administering 4-FA in case of bladder dysfunction or vomiting.

This is probably not a compound to use while working or committing oneself to other important duties requiring a clear head and normal appearance.

4-MEC 

4-MEC seems to be extremely active in doses of 75 mg and up when taken by more direct routes of administration. Oral doses may require 100 mg or greater for this level of effects.

Its effects are very comparable to pure MDMA. Its stimulant properties are accompanied by empathogen properties which are equally strong if not stronger. 

The 4MEC experience could be described as a tweaky "roll"-like experience, which lasts a couple hours (typically not as long lasting as molly).

Some of the highest quality 4-MEC typically appears in the form of crystalline shards (small and large), which break into a sandy powder. This compound seems to dissolve fine in water, but not as readily or easily as the more powdery RC's (such as 2-FMA or 4-FA).

4-MEC produces an often overwhelming rush and an "instant roll" when administered by more direct routes. This is a very active chemical and should be handled/used with extra caution.

Nausea is likely and may be intense, but subsides after vomiting.

This is definitely not a compound to use while working or committing oneself to other important duties requiring a clear head and normal appearance.

Diphenylpyrrolidines

The compounds below are sometimes available as research chemicals and have been sold as designer drugs. They share structural similarities with drugs of the piperidine family such as methylphenidate and desoxypipradol, as well as N-pyrrolidinyl-cathinones such as MDPV and a-PVP. They also share some interestingly similar characteristics in their mode of action and subjective effects.

D2PM

D2PM Molecule

D2PM is a long acting stimulant which has been sold as a research chemical and designer drug. It is alternately known as diphenylprolinol.

D2PM is an NDRI with a mode of action similar to desoxypipradol and methylphenidate. 

Structurally related to pipradol and desoxypipradol, but contains a pyrrolidine ring in place of a piperidine ring. Being a chiral compound, the dextro-rotatory enantiomer [(R)-(+)] is the most pharmacologically active.

Long acting compound. Its effects generally last 5 to 8 hours.

Due to its long duration, dose accumulation may be an issue; especially when combined with its potential to produce a state of "tweaky" over-stimulation.

Noteable adverse effects include paranoia, anxiety, myoclonus, psychosis, hallucinations, delerium due to lack of sleep, and a state of prolonged agitation lasting days after use. Adverse effects with long term use may include neuro/cardio-toxicity, and physical/psychological habituation.

desoxy-D2PM

desoxy-D2PM Molecule

Desoxy-D2PM is a stimulant compound which has been sold as a research chemical and designer drug. It is

alternately known as 2-diphenylmethylpyrrolidine.

Desoxy-D2PM is an analogue of diphenylprolinol, differing only with the absence of a hydroxyl group at the carbon-2 position. It is related to diphenylprolinol in the same way that desoxypipradol is related to pipradol.

Its mode of action is similar to related compounds; desoxy-D2PM is a norepinephrine-dopamine reuptake inhibitor.

It's effects are similar to diphenylprolinol as well as desoxypipradol. 

It has been reported to possess some of the same downsides as its relative 2-DPMP; with adverse effects being characterized by agitation, anxiety, paranoia, prolonged insomnia, and compulsiveness. These characteristics are shared by its distant relatives of the N-pyrrolidinyl substituted cathinone family, specifically MDPV and a-PVP. 

Adverse effects with long term use may include neuro/cardio-toxicity, and physical/psychological habituation.

Rolling, Rolling, Rolling - Stimulating Empathogens of the MDMA Type

Methylone:

Basic:

Source: Erowid.org

Other common names include bk-MDMA, M1, or MDMC. Methylone is a substituted cathinone with empathogen and stimulant properties. It may be considered an analogue of MDMA as well as methcathinone.

This drug is very similar to MDMA, not only chemically, but in its mode of action as well as well. Methylone had originally been researched and patented as an antidepressant in the 1990's, but was never marketed commercially.

Chemistry:

Put simply, methylone is the beta-ketone analog of MDMA (ecstasy). It is related to methcathinone in the same way MDMA is related to methamphetamine. It is best described as an analog of MDMA where the beta carbon contains a ketone group.

Mode of Action:

Methylone is believed to induce the release of the monoamine neurotransmitters while inhibiting their reuptake as well; leading to increased flow of monoamine transmission throughout the brain and CNS. Its affinity for the serotonin transporter is somewhat lesser than that of MDMA, while its affinity for dopamine and norepinephrine transporters is comparable to MDMA. 

Effects:

Based on its pharmacological profile, methylone is likely to produce moderate empathogenic effects, with strong euphoric-stimulant effects similar to MDMA.

Butylone

Basic:

Butylone is a compound of the substituted cathinone family and is also known as bk-MBDB. It produces stimulant and mild enactogen effects and has been sold as a research chemical. 

Chemistry:

Butylone is the chain lengthened homologue of methylone (bk-MDMA). It differs from methylone in that it contains an ethyl rather than a methyl group at the alpha carbon. Butylone is also the beta-keto homologue of MBDB.

Mode of Action:

Butylone produces stimulating enactogenic effects. Its mode of action involves potentiation of monoamine pathways, presumably through inhibition of serotonin, norepinephrine, and dopamine reuptake transporters and possibly through increased monoamine release.

Effects:

Users have reported predominantly stimulant reactions, though its effects have also been compared to methylone (though higher relative doses are required), as well as MDMA. Positive results have been reported with a combination of butylone and methylone. Jaw tension or grinding similar to that caused by ecstasy has been reported. There are limited reports of mild empathogenic effects. Users report an enhanced enjoyment of music and tactile sensitivity.

Side effects may include gastric distress, "tweakiness", muscle tension, and anxiety or dysphoria, all of which have been reported by some users.

Typical dosages seem to range from 25-75mg, though some have reported oral dosages of 100mg or more, while effects generally last 2-3 hours, depending largely on dose and route of administration.

Pentylone (bk-MBDP)

Basic:

Pentylone is a centrally acting compound of the substituted cathinone family with psychostimulant and euphorigenic properties. It was originally synthesized in the 1960's and is/has been marketed as a research chemical and designer drug. Pentylone was present in the original ivory wave novelty product in a 1:1 ratio with MDPV.

Chemistry:

Pentylone is the 3,4-methylenedioxy analogue of pentedrone, and can be considered the methylamino analogue of MDPV.

Mode of Action:

Pentylone is believed to act as a releasing agent and/or reuptake inhibitor of dopamine, norepinephrine, and possibly serotonin.

Effects:

The effects of pentylone are comparable to those of other 3,4 methylenedioxy-cathinone-type stimulants (i.e. stimulating and enactogenic), and last 2 to 3 hours. It can be taken by oral, intravenous, intranasal, and rectal routes. It may also be vaporized and inhaled. Users who smoke pentylone report a greater level of "tweakiness". Its effects have been compared to those of cocaine by intranasal or vaporized routes.


Reported dosages range from as low as 10mg to as high as 100mg or more; route of administration is a major factor. It can be swallowed, snorted, injected or vaporized ("smoked"). Swallowing pentylone requires significantly higher dosages.

Ethylone (MDEC, bk-MDEA) 

Basic:

Ethylone is a cathinone-based compound with stimulant, enactogen, and psychedelic properties. It is a relative of methylone and has been sold as a research chemical/designer drug. Ethylone has a very short history of human use and little is known regarding its toxicity or safety profile. 

Chemistry:

Ethylone is the cathinone equivalent to MDEA ("Eve"), and differs only in containing a ketone at the bata side chain position. 

Mode of Action:

The pharmacological profile of this compound has not been studied, though it is likely to produce its effects via potentiation of monoamine + serotonin pathways.

Effects:

Ethylone can be expected to produce effects similar to butylone or other methylenedioxy-cathinones, with typical doses seeming to range from 50-150mg based on user reports. 

According to some users, ethylone may very well be described as a less potent alternative to methylone. Ethylone is sometimes taken alongside methylone or butylone for an enhanced set of effects.

This was taken as an excerpt from my entry on Substituted Cathinones

Hawaiian Baby Woodrose (Seeds)

Hawaiian Baby Woodrose, or HBW,  is a climbing vine known by the botanical name Argyreia Nervosa. It is encountered in the Carribean, Africa, and areas of Hawaii. It bears small seeds which look very much like small chocolate chips. The seeds are often collected and consumed for the psychedelic alkaloids they contain. 

HBW seeds contain ergine, known also as lysergic acid amide or LSA, an ergoline derivative closely related to LSD.

Currently, HBW is not a controlled substance in the US, however the LSA they contain is listed as a schedule III controlled substance.

User reports on HBW seeds suggest that not many seeds are required for an effect. Psychedelic effects become apparent with 4 or more seeds eaten on an empty stomach.

LSA is believed to act similarly to most classical hallucinogens; It is likely to exhibit agonist and/or partial agonist activity at multiple serotonin receptors, including the 5HT-2A subtype.

The effects of LSA are similar to the effects of LSD, and are reported to be less intense. The experience typically lasts 6 to 8 hours, though a pleasant afterglow may linger for up to 12 hours.

Psychological effects of LSA include Introspection, Altered cognitive process, Laughing or an urge to laugh, Closed or open eye visual distortions such as spots, light tracers, color shifting, distortion of surface textures, brightened or enhanced colors, Enhancement of sensory input such as taste, smell, sound, or vision, and Time distortion. Physiological effects include Dilated pupils (mydriasis), Increased heart rate, CNS stimulation or sedation, Insomnia, Stomach pain or cramps, and Mild to severe nausea and vomiting (some reccommend taking a regular dose of dimenhydrinate or diphenhydramine 30 minutes before consuming the seeds).

Likely After-Effects include Possible "hangover" characterized by blurred vision with vertigo or dizziness, and an ability to acheive a deep or refreshing sleep following the experience.

ACLU Makes Biggest Effort Yet to Assess Growth of America's Police State

The American Civil Liberties Union has filed 255 public records requests in 23 states, as well as with the Army National Gaurd, in order to examine the increasing militarization of state, county, and local police departments. Read more here and here.

Biological Actions of Various Pyrovalerone-Family Compounds on Monoamine Systems

Very Potent NDRI's Indeed:

Ki Values indicate binding affinity

IC50 values indicate level of intrinsic activity (measured by the amount of a given compound it takes to inhibit the function of a monoamine transporter by 50%)

DAT/DA = Dopamine 

NET/NE = Norepinephrine

SERT/SER = Serotonin

Cocaine (Reference Standard)
DAT Ki: 432 ± 29
DA IC50: 461 ± 46

NET Ki: 2150 ± 190
NE IC50: 378 ± 48

SERT Ki: 358 ± 24
SER IC50: 494 ± 51

APVP
DAT Ki: 33.7 ± 5.4
DA IC50: 52.3 ± 6.2

NET Ki: 199 ± 45
NE IC50: 56.0 ± 13

SERT Ki: >10µM
SER IC50: ???

Pyrovalerone (Racemic)
DAT Ki: 21.4 ± 4.6
DA IC50: 52.0 ± 20

NET Ki: 195 ± 26
NE IC50: 28.3 ± 8.1

SERT Ki: 3770 ± 560
SER IC50: 2780 ± 590

S-Pyrovalerone 
DAT Ki: 18.1 ± 3.0
DA IC50: 16.3 ± 2.3

NET Ki: 109 ± 45
NE IC50: 11.3 ± 2.4

SERT Ki: 2220 ± 550
SER IC50: 1070 ± 230

Naphyrone
DAT Ki: 20.1 ± 7.1
DA IC50: 40.0 ± 13

SERT Ki: 33.1 ± 1.1
SER IC50: 46.0 ± 5.5

NET Ki: 136 ± 27
NE IC50: 11.7 ± 0.9

3,4-Dichloropyrovalerone 
DAT Ki: 11.5 ± 1.4
DA IC50: 43.0 ± 20

SERT Ki: 199 ± 50
SER IC50: 600 ± 63

NET Ki: 37.8 ± 3.2
NE IC50: 21.0 ± 0.6


Meltzer PC, Butler D, Deschamps JR, Madras BK. 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. Journal of Medicinal Chemistry. 2006 Feb 23;49(4):1420-32.

PMID: 16480278
DOI: 10. 1021/jm050797a

Generic Suboxone? What happened?

For roughly 4 years we've awaited a generic version of Suboxone to become available. 

However, by the time the patent expired on the original Suboxone tablets, Reckitt Benckiser (its manufacturer) had aquired an exclusive new patent, on an exclusive, new form of their product. Their new product was Suboxone film; the same medication, only rather than in tablet form, it came in the form of paper-thin film strips, each enclosed in a plastic wrapper.

Around the same time, in order to avoid generic competitors from introducing a cheaper suboxone tablet to the market, RB took some bold measures; first, they convinced private insurers that their former tablet formulation of Suboxone was unsafe, and emphasized the possibility of the tablet being consumed by young children. 

They introduced the "new and improved" formulation; film strips, each individually wrapped in a child-proof container. RB convinced many insurers that they should no longer provide coverage for the tablet formulation (or at least not without the doctor justifying, in writing, why the tablet form was nessessarry), and that they should exclusively cover the new, patent-protected film formulation, which only their company could produce.

Insurance providers bought it. Subsequently, the manufacture and marketing of a generic suboxone became unappealling, due to the limited profits it would produce (remember, RB convinced many insurers to only cover the new version of the drug). This bought some time, and further delayed the possibility of a generic being introduced to the market. 

Roughly 3 years later, RB sent a CITIZENS PETITION to the FDA claiming that its original product (the tablets) was a "bad drug", and requesting that a ban be placed on its manufacture and sale, in order to "protect the public" from their previous tablet formulation. 

Had the FDA granted this request, all generic manufacturers would have been prevented from ever introducing a generic suboxone tablet (a prospect which, until that point, would have been inevitable). RB would have been left to dominate the market, with an overpriced and overhyped, patent protected, suboxone film.

However, in recent days, the FDA denied Reckitt's petition. Long story short; the door remains open for a generic product to be made available. When or if this will happen is another question - though it's quite likely  to happen in the near future, as RB has as of mid-march discontinued the tablet formulation of suboxone. In the meantime, the film is available in two new dosages; one containing 4 mg buprenorphine, and another containing 12 mg buprenorphine.

Read more here

Piperazines

BZP

Known chemically as benzylpiperazine. BZP is a psychostimulant compound and a derivative of piperazine. 

Its use was documented in clinical literature as early as the 1950's; more recently it has appeared as a research chemical and recreational drug. It became a popular grey market/"legal high" product in the US and elsewhere in the early 2000's but has since been listed as a schedule 1 controlled substance in the US. Its effects are similar to amphetamine or methamphetamine.

BZP acts as a mild to moderate releaser of dopamine and norepinephrine, and a weak serotonin releaser. It is also thought to inhibit the reuptake of serotonin, norepinephrine, and dopamine. 

The oral route has been common for BZP users, with dosages up to 150 mg. Its effects last several hours.

Adverse effects have included kidney damage and seizures.

TFMPP

Chemically known as trifluoromethylphenylpiperazine. TFMPP is a piperazine derivative and an analogue of BZP. It has been marketed as an MDMA alternative. It was temporarily listed as a controlled substance in the US through the DEA's emergency scheduling procedure, but the ban was allowed to expire without renewal.

It differs pharmacologically from benzylpiperazine in that it produces enactogen effects rather than stimulant-enactogen effects. Its monoaminergic action is almost exclusively serotonergic. TFMPP binds to multiple 5HT receptor subtypes as a full agonist, and shows partial agonist efficacy at the well known 5HT2A subtype. It is also a serotonin reuptake inhibitor/releasing agent, with little to no effect on dopamine or noradrenaline.