In the Eyes of God said:
Thanks bud. I figure they'd all been studied. Thats not really a problem. At least it hopefully identifies the pharmacology and sets the foundation for barb SAR data.
I guess they don't get very potent neither which is a shame. Im always wishing every drug had its "fentanyl" group hidden deep in the literature somewhere. Like PCP analogs that are 5,000x stronger, id jizz my pants at the sight of that since PCP's by far my favorite substance.
I guess barbs are very similar to benzos, and I bet benzos have stronger analogs eh? Although don't know jackshit about benzos neither. I assume there's a whopload of SAR data for benzos as well, just like opioids. I swear fentanyl SAR data is the most straightforward, predictable shit imaginable. Except for that Lofentanil which incredibly took the duration from maybe 60 minutes for regular fent, to something like 1.5-3 days. Wouldn't even want something that long though. You overdose your fucked. You'd need an IV bag of naloxone to stay alive.
I guess barbs aren't all that interesting hence why little discussion anymore
First, have you tried ketamine? I have found it more euphoric than PCP when done iv, and even though it doesn't last that long, it seems to make me feel more connected to the universe than any other drug I have tried, and since ketamine seems to be a more complete sensory anesthetic (in the sense of eliminating all sensory input and causing the user to experience the sense of being only a mind) IME I awaken with the sense that I have been meditating in a complete and intense way.
But back to barbs and opioids: almost all opioids require multiple injections of naloxone to keep the patient from returning to a state of bradypnea because of two things: naloxone is only effective for only about 30-90 minutes (when not given in intentionally cruel excess); and, after an antagonist wears off, the receptor/ second messenger(s) transduction system(s) are hypersensitive to remaining systemic opioids, and drugs like methadone, especially in opioid naive adults and children, most often require 24 hours or more or naloxone in order to maintain a state of eupnea (normal respiration.)
Barbiturates --pronounced bar-bit-CHUR-ates and not bar-bit-CHOO-its: this is one of my pet peeves with medical students and physicians-- bind at an allosteric site completely different than the omega receptors where benzodiazepines bind. Now benzodiazepines and barbiturates both affect chloride channels (which hyperpolarize the neuron, making it more difficult to elicit an action potential.) But while benzodiazepines affect the binding of GABA at the GABA-A/omega receptor complex which then causes chloride channels to open ephemerally (benzodiazepine agonists cause increased GABA binding to the GABA-A/omega receptor complex), barbiturates putatively cause the chloride channels to open directly and allow them to remain open while the drug is present. This is one of the reasons that barbiturates are so much more dangerous than benzodiazepines, along with two other unusual and very uncommon characteristics of barbiturates: no antagonist is known to exist, and the tolerance to barbiturates increases without a parallel increase in the lethal dose.
As most of you know today, outside of injectable pentobarbital (Nembutal ®) in veterinary medicine and pharmaceutical research; butalbital (Fioricet®), phenobarbital and mephobarbital in allopathic medicine; and the highly lipophilic thiobarbiturates thiopental sodium (Sodium Pentothal®) and sodium thiamyl, which are still used in surgical anesthesia, albeit more and more infrequently as continuous infusion agents with higher therapeutic indices like propofol (Diprovan ®) become more common; most other once ubiquitous barbiturates like secobarbital (Seconal ®), amobarbital (Amytal ®) and a combination of the two (Tuinal ®) are very difficult to obtain iatrically. Even a recent order for injectable Seconal® from my veterinary distributor--which once was commonplace in my practice--recently came back as
no longer available, whereby I was directed to a research distributor to make the purchase. This is not a logistics problem since my license allows for even Schedule I drugs to be used for research purposes. (Note that all the injectable and short-acting barbiturates mentioned here are CII and all the thiobarbiturates are CIII. The moderate duration barbiturates like butalbital are CIII, and long acting barbiturates like phenobarbital are CIV.) However, the cost of research drugs from the oligopoly of companies allowed to sell CI and CII drugs like Sigma-Aldrich, when compared to the exact same amount of a compound for therapeutic use, is often 5-10 times as expensive as the same drug. (Also, I feel it necessary to point out that even though many people complain of the cost of new drugs and resultant drug company profits, their anger is misdirected and should be focused at both the FDA and US Patent Law, and the exorbitant costs and length of time of bringing drugs to market combined with the limited amount of time left in which a drug discoverer can be the sole producer of the drug: there are usually around 7 years left on the average 17-19 year patents by the time the FDA allows the drug to be sold in the US. This keeps smaller companies from entering the marketplace and reduces competition by limiting similar new drugs related pharmacologically from being discovered and released.) But after the patent runs out, the cost of therapeutic drugs is remarkably inexpensive when considering that if one were to try to produce any of these drugs yourself from the best price available precursors, you would realize how ridiculously cheap $4 prescriptions at Walmart for older generics really is.
Back to unusual barbiturates, there are no barbiturates that are or were on the market that were out of the ordinary. The short-acting category of pentobarbital and secobarbital are IMHO, the most euphorigenic barbiturates. The intermediate and long-acting barbiturates, and the ultra-short acting thiobarbiturates, are not particularly enjoyable to me in any way (although one acquaintance of mine seems to like long-acting phenobarbital for some reason.) But, if you look at drugs like methaqualone or glutethimide, which IMO are dopamine reuptake inhibitors at the DAT or VMAT-2, or have some other unusual interaction with dopamine when compared to most other sedative/hypnotics (other than their GABA-A/omega interactions), then there may be a barbiturate of an atypical structure which also may affect dopamine in a different way, and is more like a quinazoline type drug like methaqualone (Quaalude ®) or a carbamate type drug like glutethimide (Doriden ®). But currently, while one may have already been synthesized, its extreme euphorigenic effects are not widely known.
MobiusDick
!!
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