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Mansa Musa was the ruler of the Mali Empire in West Africa. Details recorded here should be sourced; unknown information is left blank.
MORE →Reflects the personal views, recollections, and perspective of the author, Mike Davis.
This is a personal recollection on the Move fire on May 13, 1985
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| Other names | RB64; 22-Thiocyanatosalvinorin A |
| Drug class | Irreversible κ-opioid receptor agonist |
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| Formula | C24H27NO8S |
| Molar mass | 489.54 g·mol−1 |
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RB-64, also known as 22-thiocyanatosalvinorin A, is a semi-synthetic derivative of salvinorin A. It is an irreversible agonist, with a reactive thiocyanate group that forms a bond to the κ-opioid receptor (KOR), resulting in very high potency.[1] It is functionally selective, activating G proteins more potently than β-arrestin-2.[2] RB-64 has a bias factor of up to 96 and is analgesic with fewer of the side-effects associated with unbiased KOR agonists.[3] The analgesia is long-lasting. Compared with unbiased agonists, RB-64 evokes considerably less receptor internalization.
 | This analgesic-related article is a stub. You can help Wikipedia by adding missing information. |
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RB-64, also known as 22-thiocyanatosalvinorin A, is a semi-synthetic derivative of salvinorin A. It is an irreversible agonist, with a reactive thiocyanate group that forms a bond to the κ-opioid receptor (KOR), resulting in very high potency. It is functionally selective, activating G proteins more potently than β-arrestin-2. RB-64 has a bias factor of up to 96 and is analgesic with fewer of the side-effects associated with unbiased KOR agonists. The analgesia is long-lasting. Compared with unbiased agonists, RB-64 evokes considerably less receptor internalization.
RB-101 is a drug that acts as an enkephalinase inhibitor, which is used in scientific research. RB-101 is a prodrug which acts by splitting at the disulfide bond once inside the brain, to form two selective enzyme inhibitors and blocking both types of the zinc-metallopeptidase enkephalinase enzymes. This inhibits the breakdown of the endogenous opioid peptides known as enkephalins. These two enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP), are responsible for the breakdown of both kinds of enkephalin naturally found in the body, and so RB-101 causes a buildup of both Met-enkephalin and Leu-enkephalin. These peptides act primarily at the delta opioid receptor, although they also stimulate the mu opioid receptor to some extent through a delta-opioid receptor mediated interaction with another peptide cholecystokinin, and the enzyme-inhibiting effects of RB-101 thus produce indirect stimulation of both of these opioid receptor subtypes. This causes RB-101 to be strongly synergistic with cholecystokinin antagonists, such as proglumide. Unlike the more commonly used enkephalinase inhibitor racecadotril, which only acts peripherally and has antidiarrheal effects, RB-101 is able to enter the brain, and thus produces a range of effects, acting as an analgesic, anxiolytic and antidepressant. The antidepressant and anxiolytic actions are thought to be mediated through the delta opioid receptor, while the analgesic effects most likely result from a mix of mu and delta activity. Animal studies suggest that RB-101 is also likely to be useful in relieving the symptoms of acute opioid withdrawal and in the management of opioid dependence. A significant advantage of inhibiting the breakdown of endogenous opioid peptides rather than stimulating opioid receptors with exogenous drugs is that the levels of opioid peptides are only increased slightly from natural levels, thus avoiding overstimulation and downregulation of the opioid receptors. This means that even when RB-101 is used in high doses for extended periods of time, there is no development of dependence on the drug or tolerance to its analgesic effects. Consequently, even though RB-101 is able to produce potent analgesic effects via the opioid system, it is unlikely to be addictive. Unlike conventional opioid agonists, RB-101 also failed to produce respiratory depression, which suggests it might be a much safer drug than traditional opioid painkillers. RB-101 also powerfully potentiated the effects of traditional analgesics such as ibuprofen and morphine, suggesting that it could be used to boost the action of a low dose of normal opioids which would otherwise be ineffective. RB-101 itself is not orally active and so has not been developed for medical use in humans, however modification of the drug has led to newer orally acting compounds such as RB-120 and RB-3007, which may be more likely to be adopted for medical use if clinical trials are successful.
RB-120 (benzyl (2S)-2-{[(2S)-2-({[(2S)-2-amino-4-methylsulfanylbutyl]disulfanyl}methyl)-3-phenylpropanoyl]amino}propanoate) is an orally active analog of the drug RB-101. It acts as an enkephalinase inhibitor, which is used in scientific research. Via intravenous administration, it is approximately three times as potent as RB-101 or twice as potent as the isolated (S,S) isomer of RB101. However, via i.p. administration it is approximately twice as potent as racemic RB-101 and about as potent as the isolated (S,S) isomer of RB101. During i.v. administration RB120 is approximately twice as weak as morphine in terms of analgesia; however, it is 16x weaker during i.p. and p.o. administration.
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and psychotic behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco. Adverse effects may include paranoia, addiction, and an increased risk of suicide, as well as seizures and coma in cases of overdose. Flashbacks may occur despite stopping usage. Chemically, PCP is a member of the arylcyclohexylamine class. PCP works primarily as an NMDA receptor antagonist. PCP is most commonly used in the US. While usage peaked in the US in the 1970s, between 2005 and 2011, an increase in visits to emergency departments as a result of the drug occurred. As of 2022, in the US, about 0.7% of 12th-grade students reported using PCP in the prior year, while 1.7% of people in the US over age 25 reported using it at some point in their lives.
Before the 1921 destruction of Tulsa’s Greenwood District, Black residents had created a remarkable center of business and community life. The district included stores, professional offices, entertainment venues and homes owned by Black citizens. Understanding Greenwood means learning what was built—not only what was burned.
MORE →Brown v. Board of Education in 1954.
