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Bretisilocin
Bretisilocin, also known by its developmental code name GM-2505 and as 5-fluoro-''N''-methyl-''N''-ethyltryptamine (5F-MET or 5-fluoro-MET), is a serotonergic psychedelic of the tryptamine family which is under development for the treatment of major depressive disorder. It is an analogue of dimethyltryptamine (DMT) and is the 5-fluorinated derivative of methylethyltryptamine (MET). Bretisilocin's route of administration is intravenous infusion. The drug acts as a potent and well-balanced serotonin 5-HT2A and 5-HT2C receptor agonist, serotonin 5-HT2B receptor antagonist, and serotonin releasing agent. It produces psychedelic-like effects in animals and similarly produces robust hallucinogenic effects in humans. The duration of bretisilocin is 60 to 90minutes and is intermediate between the durations of DMT and psilocybin. It has been regarded by its developer as an improvement of DMT. Bretisilocin is under development by Gilgamesh Pharmaceuticals. As of March 2024, it is i ...
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Gilgamesh Pharmaceuticals
Gilgamesh Pharmaceuticals is a pharmaceutical company that is developing psychedelic and related drugs as medicines. It is a "discovery stage" company and is focused on developing new chemical entities. Its drug candidates include the ketamine-related NMDA receptor antagonist blixeprodil (GM-1020; (''R'')-4-fluorodeschloroketamine or (''R'')-4-FDCK), the dimethyltryptamine (DMT)-related serotonergic psychedelic bretisilocin (GM-2505; 5-fluoro-''N''-methyl-''N''-ethyltryptamine or 5F-MET), the noribogaine-related κ-opioid receptor agonist GM-3009, and the non-hallucinogenic psychoplastogen GM-5022. Another potential candidate is GM-2040, a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist. The company was co-founded by Jonathan Sporn, Jeff Witkin, Dalibor Sames, Andrew Kruegel, and Mike Cunningham. Cunningham is a research scientist at Gilgamesh. Sames, Kruegel, and Cunningham have worked together at Sames's lab at Columbia University. In May 2024, AbbVie mad ...
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Intravenous Administration
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use. The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route of administration is also used for the consumpt ...
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Chemical Derivative
In chemistry, a derivative is a compound that is derived from a similar compound by a chemical reaction. In the past, derivative also meant a compound that ''can be imagined to'' arise from another compound, if one atom or group of atoms is replaced with another atom or group of atoms, but modern chemical language now uses the term structural analog for this meaning, thus eliminating ambiguity. The term "structural analogue" is common in organic chemistry. In biochemistry, the word is used for compounds that at least theoretically can be formed from the precursor compound. Chemical derivatives may be used to facilitate analysis. For example, melting point (MP) analysis can assist in identification of many organic compounds. A crystalline derivative may be prepared, such as a semicarbazone or 2,4-dinitrophenylhydrazone (derived from aldehydes or ketones), as a simple way of verifying the identity of the original compound, assuming that a table of derivative MP values is avail ...
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Intravenous Administration
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use. The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route of administration is also used for the consumpt ...
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Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, pharmaceutical drug, drugs, medical nutrition therapy, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received institutional review board, health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small Pilot experiment, pi ...
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Phases Of Clinical Research
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ...
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Psilocybin
Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P. cyanescens'', but psilocybin has also been isolated from about a dozen other genera. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks. Imagery found on prehistoric murals and rock paintings of modern-day Spain and Algeria suggests that human usage of psilocybin mushrooms predates recorded history. In Mesoamerica, the mushrooms had long been consumed in spiritual ...
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Duration Of Action
Pharmacodynamics (PD) is the study of the biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for example, infection). Pharmacodynamics and pharmacokinetics are the main branches of pharmacology, being itself a topic of biology interested in the study of the interactions between both endogenous and exogenous chemical substances with living organisms. In particular, pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects. Pharmacodynamics is sometimes abbreviated as PD and pharmacokinetics as PK, especially in combined reference (for example, when speaking of PK/PD models). Pharmacodynamics places particular emphasis on dose–response relationships, that is, the relationships ...
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Hallucinogen
Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants. However, certain hallucinogens such as Fly agaric as well as other gabaergic hallucinogenics are more often considered to technically be hypnotics, therefore indicating another separate subcategory of drugs which can substantially alter visual perception. Etymology The word ''hallucinogen'' is derived from the word ''hallucination''. The term ''hallucinate'' dates back to around 1595–1605, and is derived from the Latin ''hallūcinātus'', the past participle of ''(h)allūcināri'', meaning "to wander in the mind." Characteristics Leo Hollister gave five criteria for classifying a drug as hallucinogenic.Glennon RA. Classical drugs: an introductory overview. In Lin GC and ...
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Serotonin Releasing Agent
A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons. SSRAs have been used clinically as appetite suppressants, and they have also been proposed as novel antidepressants and anxiolytics with the potential for a faster onset of action and superior efficacy relative to the selective serotonin reuptake inhibitors (SSRIs). A closely related type of drug is a serotonin reuptake inhibitor (SRI). Examples and use of SRAs Amphetamines like MDMA, MDEA, MDA, and MBDB, among other relatives (see MDxx), are recreational drugs termed entactogens. They act as serotonin-norepinephrine-dopamine releasing agents (SNDRAs) and also agonize serotonin receptors such as those in the 5-HT2 subfamily. Fenfluramine, chlorphentermine, and aminorex, which are also am ...
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Serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction. Approximately 90% of the serotonin that the body produces is in the intestinal tract. Biochemically, the indoleamine molecule derives from the amino acid tryptophan, via the (rate-limiting) Tryptophan hydroxylase, hydroxylation of the 5 position on the ring (forming the intermediate 5-Hydroxytryptophan, 5-hydroxytryptophan), and then Aromatic L-amino acid decarboxylase, decarboxylation to produce serotonin. Serotonin is primarily found in the enteric nervous system located in the human gastrointestinal tract, gastrointestinal tract (GI tract). However, it is also produced in the central nervous system (CNS), specifically in the raphe nuclei located in the brainstem, Merkel cells located in the skin, Neuroendocrine cell#Pulmo ...
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Potency (pharmacology)
In the field of pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemi ..., potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug (e.g., fentanyl, alprazolam, risperidone, bumetanide, bisoprolol) evokes a given response at low concentrations, while a drug of lower potency ( meperidine, diazepam, ziprasidone, furosemide, metoprolol) evokes the same response only at higher concentrations. Higher potency does not necessarily mean greater effectiveness or more side effects. The IUPHAR has stated that 'potency' is ''"an imprecise term that should always be further defined"'', for instance as EC_, IC_, ED_, LD_ and so on. See also * Reaction inhibitor § Potency References F ...
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