The Benzomorphans are a family of tricyclic opioid drugs that also highly likely to be NMDA antagonists (dissociatives) at the same time1 2 3. They have been recorded to yield hallucinations with several qualities of the experience consistent with the familiar hallucinatory dissociative experience (in addition to their opioid effects). Benzomorphans have a spotty history of human use, though two have been marketed and sold as prescription medications for treatment of pain. They are very rarely prescribed in western countries nowadays. The two that made it to the market are Pentazocine and Phenazocine, under the brand names Talwin and Prinadol/Narphen respectively. Hallucinations have also been observed in more experimental drugs like Cyclazocine and Alazocine.
 |
| The generalized structure of a hallucinogenic Benzomorphan (stereochemistry may vary) |
The exact receptor profile of Benzomorphans is variable. As a whole family they are mixed agonists/antagonists of the various CNS opioid receptors, which yields a variety of effects4. Agonism of the μ-opioid receptor yields most of the familiar opioid effects like analgesia and sedation. Most familiar opioids primarily act on this receptor. Agonism of the other two receptors is much less common. Agonism of the δ-opioid receptor also yields therapeutic pain relief but is very rare as a primary method of action. Agonism of the κ-opioid meanwhile, triggers interesting effects like dysphoria and hallucinations in addition to some standard opioid effects. A very familiar and notorious κ-opioid agonist is Salvinorin A, the active constituent in Salvia divinorum. Also noteworthy is the fact that activation of the κ-opioid receptor seems to suppress activity of the μ-opioid receptor5. This turns the degree to which different drugs act as agonists for the different receptors into a complex balancing act, juggling effects between the receptors selectively. Subtle changes to these molecules can yield shifts in this delicate opioid receptor balance6. However, most hallucinogenic Benzomorphans are primarily regarded as κ-opioid agonists, and thus to some degree μ-opioid antagonists (though this varies, Phenazocine for example, is a μ-opioid agonist).
Some benzomorphans are observed to be NMDA antagonists, though it is unknown if all of the hallucinogenic benzomorphans have this effect, it is highly likely that they do1 2 3. Cyclazocine is at the very least confirmed to be an NMDA antagonist7. Many of them are also very likely σ receptor agonists, a property shared with a wide variety of stimulants and dissociatives including PCP, Ketamine, DXM, Cocaine, and Methamphetamine8. It is still unknown what exactly σ agonism specifically entails or what the effects are, as most agonists also act on a variety of other receptors. It nonetheless probably plays some role in the effects of these various drugs, perhaps as a psychotomimetic?
The picture this paints of Benzomorphans is that of a hallucinogenic opioid with notable analgesic effects in addition to hallucinatory κ-opioid effects, similar to Salvia. On top of this is probable NMDA antagonism, which would give an extra degree of dissociative hallucinatory effects on top of that. This would be an extremely unique hallucinatory experience, quite unlike that of any known hallucinogens- a great deal of physical dissociation and anesthesia with intense and vivid open and closed eyed visuals.
It should be noted that hallucinations have been attributed to a wide variety of opioids9-however most other opioids have seen significantly more widespread use than pentazocine, thus a much larger body of data. Hallucinations from other opioids are still considered relatively rare, despite the much larger data set. What stands out about Benzomorphans is their unique receptor profile and the frequency in which hallucinations are reported despite a comparatively minuscule data set.
That sounds like a messy cocktail of effects nonetheless- are Benzomorphans safe? Especially considering the notorious lethal respiratory depression effects seen in opioids? Studies on the safety profiles of Benzomorphans are mostly focused on Pentazocine, as it is the most commonly prescribed one. Pentazocine acts primarily as an agonist of the κ- and δ-opioid receptors and is a weak antagonist of the μ-opioid receptor10. Respiratory depression has indeed been observed in Pentazocine, though not to the same degree of frequency and severity as with typical opioids. However, a 20 mg mg dose in a clinical study was equivalent in (still safe and tolerable) respiratory depressive effects of a 10 mg dose of morphine in a 70 kg individual11. It is worth noting that morphine is generally considered one of the "safer" opioids in terms of overdose danger, with a higher dose required to incur dangerous effects. Pentazocine also did not have a cumulative effect on respiratory depression with repeated doses11. There do exist case reports of severe respiratory depression from Pentazocine, though they cite the old age of the patients as a major risk factor and conclude that while possible, dangerous respiratory depression is rare (though this report is very early in the drug's history)12. In fact, it is believed that Pentazocine has a "ceiling effect", whereas the respiratory depressant effects max out at a certain point and no longer increase with increasing dosage. The only reported deaths from Pentazocine were from intentional overdose as a method of suicide15, or when potentiated with an antihistamine15. Respiratory depression has also been observed in Phenazocine, which saw equivalent respiratory depressant effects to Morphine16. A set of case reports stated that the dangers of respiratory depression in Phenazocine were negligible, though this was also a very early study in the drug's history17. Phenaozcine however, unlike Pentazocine is understood to be a μ-opioid agonist, so respiratory depression similar to other opioids is expected (more on that later). Curiously, dangerous respiratory effects typically arise from μ-opioid agonists, κ-opioid agonists are not understood to cause respiratory depression, and δ-opioid agonists only do it to a minor degree18. So where is this activity arising from in the Benzomorphans, when they are mostly understood to be both κ-opioid agonists and mild μ-opioid antagonists? As μ-opioid antagonists, it is likely that Benzomorphans would suppress the effects of other typical opioids if they were administered simultaneously. Indeed Pentazocine is not known to fully suppress respiratory depression from morphine when taken concurrently19. Certain Benzomorphans have also been researched extensively for their potential for treating opioid addiction through their μ-opioid receptor antagonist activity.
What about other physical side effects that opioids are known to cause- things such as itching, hypotension (low blood pressure), bradycardia (slow heart rate), sedation, nausea, and constipation? Pentazocine was observed to actually raise blood pressure and increase heart rate, similar to a stimulant11. This may be because of possible underlying NMDA antagonist effects. It also causes constipation and nausea, but does not cause the "pinpoint pupils" typical of other opioids11. Other side effects are less understood. In general, best harm reduction practices would be to avoid combining Benzomorphans with any other depressants, particularly benzodiazepines or alcohol (which aside from respiratory depression risk inducing sleep and nausea at the same time, which risks choking on vomit while sleeping). They also should not be combined with anticholinergics as this risks potentiating the drug past predictable effects for a given dose.
What about the other big danger associated with opioids: Dependence and addiction? There are few records of addiction due to Benzomorphans, though this may just be because their use is so rare. For what its worth, with a large population pool you inevitably find people becoming dependent on any drug, even ones that seem impossible to develop reinforcing behavior like high doses of DPH. One case study cites a woman who became dependent on injecting Pentazocine after being prescribed an intravenous formulation for Migraine (which resulted in severe infections of the injection sites and eventual necrosis of the hand that required amputation)20. Another case study cited a woman with bone pain who began abusing Pentazocine injections for its "Euphoric effect"21. Thus Benzomorphans do certainly have addictive potential. This fact seems to be stated that the main formulation of Pentazocine in fact contains naloxone so that it cannot be injected for abuse. The degree of addictive potential relative to other opioids however, is not yet understood.
So if Benzomorphans are understood as drugs of abuse, what is their legal status? Well only Pentazocine and Phenazocine are explicitly scheduled as they are the only ones that were manufactured and sold. Pentazocine is a Schedule IV drug in most states in the U.S., scheduled substances with an accepted medical use and low potential for abuse (it shares this place with Prescription benzodiazepines, Tramadol, and Modafinil among others). In Illinois and South Carolina however, it is Schedule II (accepted medical use but high potential for abuse, including Cocaine and Heroin), and in Kentucky it is Schedule III (Moderate potential for abuse, including Ketamine and Anabolic Steroids). It is schedule III in international UN conventions too. Phenazocine meanwhile is broadly classified as a schedule II drug. So unfortunately, the two best known and most tested hallucinogenic Benzomorphans are pretty illegal, with very low demand and near 0 street presence. It is unlikely they will ever be encountered by most people (though Pentazocine is still widely prescribed outside the U.S., with abuse reported particularly in Nigeria).
Anyways, 21 citations in, lets finally look at the hallucinogenic effects of these unique drugs in detail.
Pentazocine
 |
| l-Pentazocine |
Yes, yes I've already said so much about Pentazocine. If you skipped the intro, here it is, quick and dirty:
Pentazocine is the most widely prescribed and used benzomorphan, prescribed for pain in situations where other opioids are indicated against. It was invented in the 1950's and saw usage in the U.S. throughout the 1970's until it eventually fell into obscurity. It is now mostly prescribed only outside of western nations. Pentazocine is a mixed opioid receptor agonist/antagonist- it is an agonist of the κ- and δ-opioid receptors and is a weak antagonist of the μ-opioid receptor9. It is also likely an NMDA antagonist. Where its prescribed more commonly, most notably in Nigeria, it is known as a drug of abuse, documented in a number of case studies that demonstrate symptoms typical of opioid dependence20 21. Pentazocine is normally administered either in 30 mg injections or as a 50 mg oral tablet (This is a formulation of Pentazocine/Naloxone called Talwin- the inclusion of Naloxone is to discourage abuse by intravenous administration, Naloxone is not active orally)
 |
| An example of an oral Pentazocine/Naloxone tablet (50 mg/0.5 mg) under the brand name Talwin |
Structurewise, Pentazocine is the basic Benzomorphan structure with a 3-methyl-2-butene attached to the open functional site on the nitrogen in the piperidine ring. It is sold as a racemic mixture, however the enantiomer to which most of its opioid activity is attributed is the (-) isomer, aka l-pentazocine11.
Pentazocine is perhaps the best documented Benzomorphan for hallucinations, given its relatively widespread use. The most detailed study is a series of case reports from 1969 that give an interesting insight into this experience. It looks at a body of 7 people who experienced hallucinations out of a group of 20 people reporting adverse effects from Pentazocine. Some of the more interesting reports are as follows:
"A 74-year-old man (race not specified) was given 30 mg of pentazocine intramuscularly for pain. The patient began hallucinating and dreaming that he was being restrained."22
"A 69-year-old white man was given 60 mg of pentazocine for severe sciatica. Ten minutes later, he became groggy and complained of a "crazy feeling in the head" which was followed by severe nausea. Shortly thereafter a jerking of the muscles of his whole body developed and he said he felt that the walls of the room were beginning to move and that they were covered with multicolored designs, which he eventually recognized as a tropical forest with ferns and large white birds and peacocks which faded out and were replaced by several lions. The lions gradually faded out and were followed by geometric patterns in various colors that changed from squares to stripes and finally disappeared"22
"A 49-year-old white woman, who was given propoxyphene hydrochloride (Darvon) and aspirin but had no relief of the pain caused by infected teeth, was then given 30 mg of pentazocine intramuscularly. Vertigo and dizziness developed within 10 minutes, drowsiness in 20 minutes, and severe vomiting 40 minutes later. About 90 minutes after injection, the patient became hallucinatory and described the feeling that her ghost left her body, walked around her prone figure, and stayed with her three to four hours. She felt as if she was trying to climb the side of a huge rubber balloon, but repeatedly fell to the floor. She recalled seeing strange animals and faces but was not frightened because of the feeling of general euphoria. The next morning the patient had an apparent lack of coordination; she was unable to think clearly and was quite exhausted."22
"A white woman, age not given, received 30 mg of pentazocine intramuscularly for severe headache and experienced a floating, swirling sensation, drowsiness, and increased acuteness of hearing when her eyes were closed."22
It should be noted that there was little vocabulary to describe hallucinatory experiences beyond psychedelics in the 1960s. In previous analyses of descriptions of known dissociative hallucinogens from that era, I have taken references to "dreams" and "nightmares" as sometimes actually describing closed eyed hallucinatory experiences rather than actual sleeping dreams. They simply were not aware of the nature dissociative hallucinations at the time. Another case study from 1969 yields the following experience:
"An intramuscular injection of 30 mg of pentazocine was then given to relieve pain. Within five minutes of injection she started shaking and sweating and while waiting for a taxicab began to feel depersonalized and "freaky". En route home, she thought that the cab driver looked like a frog. For the next three hours she had visual, soundless, slow-motion hallucinations whether her eyes were open or closed. To be more accurate these were pseudohallucinations since she was aware that they were not grounded in reality. She went to bed feeling numb all over and unable to move. Five hours after the injection the hallucinations had ceased"23
This case study mentions that there was a persistent period of emotional depression for 24 hours after the hallucinations had stopped, along with uncomfortable physical effects and anxiety. It mentions other case studies where psychotic effects were observed in response to Pentazocine, such as panic, confusion, and paranoia, but not necessarily with hallucinations.
One other patient who had taken an oral dose of 75 mg described his hallucinations as:
"nice dreams, lots of sandwiches, bottles of wine, beautiful red lips"24
A seminal summary of case reports (which I believe to probably be the best paper to read on Pentazocine hallucinations) is provided by Coursey 201625. This summary offers a description of vivid auditory hallucinations too, "Visual hallucinations often consisted of various colored objects or patterns. Auditory hallucinations consisted of either voices or loud ticking of watches or clocks."25
This report also offers insight into other effects: "Closely related to tactile hallucinations are "strange feelings" reported by pentazocine-treated patients. The most frequently reported "strange feeling" was a floating or swirling sensation" "Delusional thinking was also reported with some frequency and almost invariably involved a sensation of impending death or doom. Distorted body images and feelings of depersonalization have also been noted."25
So what does this say about the nature of Pentazocine hallucinations? A lot of the effects described appear to be consistent with what is felt with dissociatives- Vertigo, dizziness, "feeling that her ghost left her body, walked around her prone figure", "She felt as if she was trying to climb the side of a huge rubber balloon, but repeatedly fell to the floor.", "apparent lack of coordination", "floating, swirling sensation", " feeling numb all over", and "distorted body images". What is most remarkable however, is the prevalence of extremely vivid open eyed hallucinations, particularly the vivid images of animals and natural scenes. One patient also cited clearly seeing intricate color geometry on the walls. This points to similarities with the best known κ-opioid hallucinogen, Salvinorin A, which can induce vivid open eyed visuals (in addition to its extreme other effects). Whether the incredibly powerful effects of Salvinorin A and hallucinations of a similar nature would present with higher doses of Pentazocine is still unknown, but it is possible that higher doses would also produce stronger dissociative or dissociative-resembling effects.
It is noteworthy that all of these case reports are for standard prescribed doses of Pentazocine, which suggests that these patients are in some way sensitive or have some underlying risk factor. It is not fully known whether increasing dosage would increase the frequency of hallucinogenic effects, but it may be possible. One study cited hallucinations in 0.6% of patients who were prescribed Pentazocine25. Another later study observes an incidence between 1-2% of patients receiving medical doses25. It noted they were most common in patients receiving oral doses of 50 mg 3-4 times a day, so this certainly suggests that higher doses increases the likelihood of hallucinations26. The only problem with pushing doses higher is that these are opioids, and that risks dangerous respiratory depression. As mentioned before, concerning respiratory depression was only noted in elderly patients with Pentazocine. While there have been overdose deaths attributed to Pentazocine, they were administered intentionally. The LD50 is given at 1000 mg/kg in rats and 205 mg/kg in mice when given orally27. In general it is understood to have a much lower risk of severe respiratory depression than typical μ-opioid agonist opioids (Morphine, Heroin, Oxycodone, Codeine etc), though the risk isn't nonexistent. Nevertheless, the study that collected case studies into one handy chart cites an oral dose of 50-240 mg as resulting in hallucinations25. One other troubling fact is that the duration is highly variable- some patients reported an onset immediately after administration, while others felt it hours later. Some only experienced hallucinations for an hour or so, while others experienced them for days or even weeks25. The majority of experiences however saw a duration of 1-5 hours25. While some found the experience euphoric, more people reported a sense of dysphoria, and a number reported a lasting sense of depression even after the hallucinatory effects had worn off, sometimes for several days25. Tread carefully.
It bears reminding that Pentazocine is a schedule IV drug in much of the U.S., making possession without a prescription illegal. It is placed in a higher schedule, schedule II, in North Carolina and Illinois, and schedule III in Kentucky. It is also internationally scheduled as a schedule III drug according to UN conventions. It's illegality in addition to its obscurity and scant history of abuse means it is highly unlikely this drug will ever be encountered by most people.
Phenazocine
 |
| l-Phenazocine |
 |
| An interesting advertisement for Phenazocine from a 1960 issue of the British Journal of Anaesthesia |
Phenazocine has a phenethyl group as the N substitution. It is notable for being significantly more potent than Pentazocine, being sold medically in the form of 5 mg oral tablets. It is believed that the phenethyl group is responsible for this steep increase in potency28. It is also administered as a racemic mixture, though the main enantiomer to which its opioid activity is attributed to is l-Phenazocine29.
There exists no information online detailing the hallucinogenic properties of Phenazocine. Rather, there is a single line on Wikipedia that states high doses may induce hallucinations. This line is parroted word for word across a variety of drug database websites that clog up any attempts to search for information about this. This claim cites a paper by Harris LS and Pearson AK from 1964, titled "Some Narcotic Antagonists in the Benzomorphan Series"30. However, reading this paper, there is no mention of hallucinations at all, for any of the drugs listed. In fact the paper is just a series of animal studies to determine analgesic effects.
So that is a dead end. The next step is to compare the receptor affinities of Phenazocine to that of known hallucinogen l-Pentazocine, to see how similar they are. l-Pentazocine has the following receptor affinity profile:
Receptor
|
Ki
(nM)
|
μ-opioid (antagonist)
|
3.9 ± 0.731
|
δ-opioid
|
49.3
± 15.131
|
κ-opioid
|
2.2
± 0.231
|
σ
|
56.6
± 7.432
|
While l-Phenazocine has the following profile:
Receptor
|
Ki
(nM)
|
μ-opioid (agonist)
|
0.2 ± 0.0429
|
δ-opioid
|
5.0 ± 0.8829
|
κ-opioid
|
2 ± 0.1329
|
σ
|
61.7 ±
10.0929
|
So what does this tell us? Well the most noteworthy difference in affinities here is with the μ-opioid receptor- Phenazocine is a μ-opioid agonist, while Pentazocine is a μ-opioid antagonist. Not only is Phenazocine a μ-opioid agonist, it is an very potent one, several times more potent than morphine. This suggests that Phenazocine would present normal opioid effects, to a high degree (hence the very low doses of its pharmaceutical formulations). Phenazocine has a significantly higher affinity for the δ-opioid receptor too, which would also contribute to opioid analgesic effects. Most important though, Phenazocine and Pentazocine have almost the same affinity for the κ-opioid receptor. This is particularly interesting when you look at the κ-opioid affinity of typical opioids, which is lower by several magnitudes. It is postulated that the hallucinogenic properties of Pentazocine arise from its high affinity for the κ-opioid receptor, something it shares with Pentazocine (They may also arise from NMDA antagonist activity but affinity for that receptor is as of now unknown for both drugs). So this tells us that it is highly likely that Phenazocine has similar hallucinogenic properties to Pentazocine. However, higher hallucinogenic doses of Phenazocine may be prohibitively dangerous courtesy of its higher affinity for the μ-opioid receptor. Simply put, you may not be able to reach a dose of Phenazocine that would induce hallucinations because it may very well kill you through respiratory depression. Perhaps this could be alleviated in a way that still allows for the hallucinogenic effects to present if a highly selective and competitive μ-opioid antagonist was administered at the same time, but this is just conjecture. This is not a risk any psychonaut should be willing to take until more information has been determined in a safe, stringent clinical setting. Meanwhile, they have a similar affinity for the σ receptor. I'm not sure what this means in terms of psychological effects, I don't know if anyone does, but it may be significant.
Of course, receptor affinities can only tell us so much, they don't account for pharmacokinetic effects and how that may affect things, but the remarkably low clinical dosages of Phenazocine indicate that these conjectures have some validity to them. But once again, the effects in humans aren't fully known until they are tested in humans, and despite the pharmaceutical use of Phenazocine, a lot of that data simply doesn't exist because its usage was so sparse and rare.
Given the illegality of Phenazocine, (It is a schedule III drug), it is unlikely any kind of development along those lines will ever occur. I would recommend staying away from this one for now, but it's certainly interesting to think about!
Cyclazocine
 |
| l-Cyclazocine |
Structurally, Cyclazocine has a cyclopropyl as the N-substitution. Like other Benzomorphans studied, l-Cyclazocine carries the opioid receptor effects while, notably, d-Cyclazocine apparently has PCP mimicking properties in animals33. This suggests possible NMDA activity in d-Cyclazocine, which raises the question if that's also the case for the d-enantiomer of other Benzomorphans. Nonetheless, similar to the other Benzomorphans, it would probably be most useful to study a racemic mixture for Cyclazocine. Indeed human trials were performed with a racemate.
It is well documented that Cyclazocine has hallucinogenic psychotomimetic effects with enough frequency that vague statements on the matter have made their way into most writing on the drug. It is mentioned in passing in two summaries on the potential for Cyclazocine to be used in treating opioid addiction, similar to how Buprenorphine would be used. One mentions "Two patients reported visual hallucinations, although one had been hallucinating before cyclazocine treatment"34, while another states
"Some persons have disturbing side effects from cyclazocine, manifesting dysphoria and vivid imagery approaching hallucinatory proportions. However, tolerance does develop for the subjective effects which can be largely eliminated by small increments in dosage, but no tolerance develops to the antagonism to opiates"35
This comment is interesting in that it states that even effects like hallucinations are mitigated with a tolerance developed from repeated dosing. The characteristics of Cyclazocine hallucinations are often defined along parameters of being "psychotomimetic". One study that recognizes them as such stated that "Some psychotomimetic phenomena such as depersonalization, peculiar, and weird experiences were as frequent for [Cyclazocine]... as for LSD."36 The fact that the tested doses induced hallucinatory effects with the same consistency of LSD is a very interesting, though possibly exaggerated statement. Nonetheless, the experience is also largely described as being dysphoric, though a few patients found it euphoric36. It notes that Cyclazocine is more incapacitating than LSD, Barbiturates, Alcohol, or Typical Opioids- attributed to its broad similarities between all of these groups of drugs, combined into one. This author however, draws parallels to scopolamine, stating "The total pattern of subjective effects was most similar to that found for scopolamine. Dry mouth, metallic taste, difficulty in swallowing, increased appetite for ice cream, impairment of memory for recent events, and restlessness occurred more frequently in scopolamine,"36 The similarities to anticholinergics listed in this example are indeed remarkable, though some of these qualia can be attributed to other hallucinatory methods of action. Another study remarked on the similarities of LSD and Cyclazocine by means of the behavioral response in rats, though it's worth mentioning that in pharmacological contexts, LSD is often regarded as a pscyhotomimetic37. This continues to hammer home the point that Cyclazocine is consistently hallucinogenic.
As far as doses are concerned, Cyclazocine is extremely potent. At an oral dose of 4 mg it is an effective μ-opioid antagonist for 24 hours, while an analgesic dose is cited at just .5 mg38. This study also states that side effects were mitigated by building tolerance, which could be driven up to 13 mg daily38. It states that hallucinatory and psychological side effects most often presented with sudden steep increases of dose- indeed one patient noted that a single 1 mg dose made them feel "unreal"38.
Safety? Cyclazocine is understood to be a clear μ-opioid antagonist38, so it definitely wouldn't have the same respiratory depressive effects as Phenazocine, but rather would probably have a similar safety profile to Pentazocine, though adjusted for its extreme potency. The potency presents the biggest hazard in using this drug, and if ever used in a recreational context, it should only be administered volumetrically or in tabs or tablets precipitated from solution.
Alazocine
 |
| (l)-Alazocine |
In animals, Alazocine produced marked psychotomimetic effects. One study noted that d-Alazocine, along with a racemate, produced behavioral responses similar to PCP in rats and squirrel monkeys, as also seen with the d-enantiomer of Cyclazocine39. This continues to point towards my hypothesis that the d-enantiomer of Benzomorphans has NMDA antagonist activity. Another study in mice (which also conjectures NMDA antagonism as a possible mechanism for what it calls Alazocine's clear hallucinogenic and psychotomimetic effects) found that Alazocine disrupts the prepulse inhibition of startle in mice, a behavioral effect seen in dissociatives40. Another study in rats found similar behavioral effects to Cyclazocine, including circling, spontaneous rearing, and bizarre side-to-side head movements41.
There is only one record of human tests of Alazocine- These tests describe Alazocine as intensely psychomimetic, to the degree that studies had to be discontinued due to the "severity" of the effects, which were likely hallucinatory. The given dose for these severe effects was 15 mg orally, for a 70 kg human42.
All of this points to Alazocine as perhaps having the highest frequency of hallucinogenic effects out of all the Benzomorphans, as most mentions of it regard it as a psychotomimetic. It is more potent than Pentazocine, with a dose probably in the range of 10-20 mg. Alazocine is also regarded as an opioid antagonist, so it likely wouldn't carry as much risk of respiratory depression.
Sources and Further Reading:
1- Grauert M, Bechdel WD, Ensinger HA, Merz H, Carter AJ (1997) Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Antagonists of the NMDA Receptor−Channel Complex. Journal of medicinal chemistry 40:2922-30.
2- Pasquinucci L, Parenti C, Amata E, Georgoussi Z, Pallaki P, Camarda V, Calò G, Arena E, Montenegro L, Turnaturi R (2018) Synthesis and Structure-Activity Relationships of (-)-cis-N-Normetazocine-Based LP1 Derivatives. Pharmaceuticals (Basel) 11(2):40
3- Grauert M, Rho JM, Subramaniam S, Rogawski MA (1998) N-methyl-D-aspartate receptor channel block by the enantiomeric 6,7-benzomorphans BIII 277 CL and BIII 281 CL. J Pharmacol Exp Ther. 285(2):767-776.
4- Turnaturi R, Marrazzo A, Parenti C, Pasquinucci L (2018) Benzomorphan scaffold for opioid analgesics and pharmacological tools development: A comprehensive review. Eur J Med Chem. 148:410-422.
5- Pan ZZ, (1998) μ-Opposing actions of the κ-opioid receptor. Trends in Pharmacological Sciences 19(3):94-98
6- Bidlack JM, Cohen DJ, McLaughlin JP, Lou R, Ye Y, Wentland MP (2002) 8-Carboxamidocyclazocine: a long-acting, novel benzomorphan. J Pharmacol Exp Ther. 302(1):374-380.
7- Sawyer DC, McLarnon JG, Church J (1995) The effects of (-)- and (+)-β-cyclazocine on NMDA-evoked responses and NMDA-mediated cell damage in cultured rat hippocampal neurons. Brain Research 698(1-2):30-38
8- Zhao J, Ha Y, Liou GI, Gonsalvez GB, Smith SB, Bollinger KE (2014) Sigma receptor ligand, (+)-pentazocine, suppresses inflammatory responses of retinal microglia. Invest Ophthalmol Vis Sci. 55(6):3375-3384
9- Sivanesan E, Gitlin MC, Candiotti KA (2016) Opioid-induced Hallucinations: A Review of the Literature, Pathophysiology, Diagnosis, and Treatment. Anesth Analg. 123(4):836-43
10- https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1606
11- Brogden RN, Speight TM, Avery GS (2012) Pentazocine: A Review of its Pharmacological Properties, Therapeutic Efficacy and Dependence Liability. Drugs 5:6–91
12- Rigas SC (1970) Severe respiratory depression after pentazocine administration: two case reports. Br J Anaesth. 42(6):547
13- Engineer S, Jennett S (1972) Respiratory depression following single and repeated doses of pentazocine and pethidine. Br J Anaesth. 44(8):795-802
14- Poklis A, Mackell MA (1982) Toxicological findings in deaths due to ingestion of pentazocine: a report of two cases. Forensic Sci Int. 20(1):89-95
15- Monforte JR, Gault R, Smialek J, Goodin T (1983) Toxicological and pathological findings in fatalities involving pentazocine and tripelennamine. J Forensic Sci. 28(1):90-101.
16- Papadopoulos CN, Keats AS (1961) VI. Comparative respiratory depressant activity of phenazocine and morphine. Clinical Pharmacology and Therapeutics 2(1):8-12
17- Thomas KB (1961) Phenazocine and Respiratory Depression. Br Med J. 1(5235):1318–9
18- Shook JE, Watkins WD, Camporesi EM (1990) Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. Am Rev Respir Dis.142(4):895-909
19- Koyyalagunta D (2007) Chapter 113 - Opioid Analgesics. Pain Management 2:939-964
20- Mudrick C, Isaacs J, Frankenhoff J (2011) Case Report: Injectable pentazocine abuse leading to necrotizing soft tissue infection and florid osteomyelitis. Hand (N Y) 6(4):457-9
21- Makanjuola AB, Olatunji PO (2010). Pentazocine abuse in sickle cell anaemia patients: A report of two case vignettes. African Journal of Drug and Alcohol Studies 8(2)
22- DeNosaquo N (1969) The hallucinatory effect of pentazocine (Talwin). JAMA 210(3):502
23- Edison GR (1969) Hallucinations associated with pentazocine. N Engl J Med. 281(8):447-448.
24- Economou G, Monson R, Ward-McQuaid JN (1971) Oral pentazocine and Phenazocine: A comparison in postoperative pain. British Journal of Anaesthesia 43(5):486-495
25- Coursey CE (1978). The Psychotomimetic Side Effects of Pentazocine. Drug Intelligence & Clinical Pharmacy 12(6), 341–346.
26- Terris B, Jick S, Beeman D, Jick H (1994). Frequency of adverse events among users of Talwin Nx. Pharmacoepidemiology and Drug Safety 3:351-354.
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