Pharmacology

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Pharmacology
Constant tempertature bath for isolated organs Wellcome M0013241.jpg
Diagrammatic representation of organ bath used for studying the effect of isolated tissues
MeSH Unique ID D010600

Pharmacology is the science of medical drugs and medications, [1] including a substance's origin, composition, pharmacokinetics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. [2] If substances have medicinal properties, they are considered pharmaceuticals.

Contents

The field encompasses drug composition and properties, functions, sources, synthesis and drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, chemical biology, therapy, and medical applications and antipathogenic capabilities. The two main areas of pharmacology are pharmacodynamics and pharmacokinetics. Pharmacodynamics studies the effects of a drug on biological systems, and pharmacokinetics studies the effects of biological systems on a drug. In broad terms, pharmacodynamics discusses the chemicals with biological receptors, and pharmacokinetics discusses the absorption, distribution, metabolism, and excretion (ADME) of chemicals from the biological systems.

Pharmacology is not synonymous with pharmacy and the two terms are frequently confused. Pharmacology, a biomedical science, deals with the research, discovery, and characterization of chemicals which show biological effects and the elucidation of cellular and organismal function in relation to these chemicals. In contrast, pharmacy, a health services profession, is concerned with the application of the principles learned from pharmacology in its clinical settings; whether it be in a dispensing or clinical care role. In either field, the primary contrast between the two is their distinctions between direct-patient care, pharmacy practice, and the science-oriented research field, driven by pharmacology.

Etymology

The word pharmacology is derived from Greek word φάρμακον , pharmakon, meaning "drug" or "poison", together with another Greek word -λογία , logia with the meaning of "study of" or "knowledge of" [3] [4] (cf. the etymology of pharmacy). Pharmakon is related to pharmakos, the ritualistic sacrifice or exile of a human scapegoat or victim in Ancient Greek religion.

The modern term pharmacon is used more broadly than the term drug because it includes endogenous substances, and biologically active substances which are not used as drugs. Typically it includes pharmacological agonists and antagonists, but also enzyme inhibitors (such as monoamine oxidase inhibitors). [5]

History

Raw opium.jpg
Naturally derived opium from opium poppies has been used as a drug since before 1100 BCE. [6]
Morphin - Morphine.svg
Opium's major active constituent, morphine, was first isolated in 1804 and is now known to act as an opioid agonist. [7] [8]

The origins of clinical pharmacology date back to the Middle Ages, with pharmacognosy and Avicenna's The Canon of Medicine , Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas. [9] Early pharmacology focused on herbalism and natural substances, mainly plant extracts. Medicines were compiled in books called pharmacopoeias. Crude drugs have been used since prehistory as a preparation of substances from natural sources. However, the active ingredient of crude drugs are not purified and the substance is adulterated with other substances.

Traditional medicine varies between cultures and may be specific to a particular culture, such as in traditional Chinese, Mongolian, Tibetan and Korean medicine. However much of this has since been regarded as pseudoscience. Pharmacological substances known as entheogens may have spiritual and religious use and historical context.

In the 17th century, the English physician Nicholas Culpeper translated and used pharmacological texts. Culpeper detailed plants and the conditions they could treat. In the 18th century, much of clinical pharmacology was established by the work of William Withering. [10] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period. [11] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues. [12] The first pharmacology department was set up by Rudolf Buchheim in 1847, at University of Tartu, in recognition of the need to understand how therapeutic drugs and poisons produced their effects. [11] Subsequently, the first pharmacology department in England was set up in 1905 at University College London.

Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts. [13] The advancement of research techniques propelled pharmacological research and understanding. The development of the organ bath preparation, where tissue samples are connected to recording devices, such as a myograph, and physiological responses are recorded after drug application, allowed analysis of drugs' effects on tissues. The development of the ligand binding assay in 1945 allowed quantification of the binding affinity of drugs at chemical targets. [14] Modern pharmacologists use techniques from genetics, molecular biology, biochemistry, and other advanced tools to transform information about molecular mechanisms and targets into therapies directed against disease, defects or pathogens, and create methods for preventive care, diagnostics, and ultimately personalized medicine.

Divisions

The discipline of pharmacology can be divided into many sub disciplines each with a specific focus.

Systems of the body

A variety of topics involved with pharmacology, including neuropharmacology, renal pharmacology, human metabolism, intracellular metabolism, and intracellular regulation Pharmacologyprism.jpg
A variety of topics involved with pharmacology, including neuropharmacology, renal pharmacology, human metabolism, intracellular metabolism, and intracellular regulation

Pharmacology can also focus on specific systems comprising the body. Divisions related to bodily systems study the effects of drugs in different systems of the body. These include neuropharmacology, in the central and peripheral nervous systems; immunopharmacology in the immune system. Other divisions include cardiovascular, renal and endocrine pharmacology. Psychopharmacology is the study of the use of drugs that affect the psyche, mind and behavior (e.g. antidepressants) in treating mental disorders (e.g. depression). [15] [16] It incorporates approaches and techniques from neuropharmacology, animal behavior and behavioral neuroscience, and is interested in the behavioral and neurobiological mechanisms of action of psychoactive drugs.[ citation needed ] The related field of neuropsychopharmacology focuses on the effects of drugs at the overlap between the nervous system and the psyche.

Pharmacometabolomics, also known as pharmacometabonomics, is a field which stems from metabolomics, the quantification and analysis of metabolites produced by the body. [17] [18] It refers to the direct measurement of metabolites in an individual's bodily fluids, in order to predict or evaluate the metabolism of pharmaceutical compounds, and to better understand the pharmacokinetic profile of a drug. [17] [18] Pharmacometabolomics can be applied to measure metabolite levels following the administration of a drug, in order to monitor the effects of the drug on metabolic pathways. Pharmacomicrobiomics studies the effect of microbiome variations on drug disposition, action, and toxicity. [19] Pharmacomicrobiomics is concerned with the interaction between drugs and the gut microbiome. Pharmacogenomics is the application of genomic technologies to drug discovery and further characterization of drugs related to an organism's entire genome.[ citation needed ] For pharmacology regarding individual genes, pharmacogenetics studies how genetic variation gives rise to differing responses to drugs.[ citation needed ] Pharmacoepigenetics studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment. [20]

Clinical practice and drug discovery

A toxicologist working in a lab Toxicology Research at FDA (NCTR 1193) (6009043040).jpg
A toxicologist working in a lab

Pharmacology can be applied within clinical sciences. Clinical pharmacology is the application of pharmacological methods and principles in the study of drugs in humans. [21] An example of this is posology, which is the study of how medicines are dosed. [22]

Pharmacology is closely related to toxicology. Both pharmacology and toxicology are scientific disciplines that focus on understanding the properties and actions of chemicals. [23] However, pharmacology emphasizes the therapeutic effects of chemicals, usually drugs or compounds that could become drugs, whereas toxicology is the study of chemical's adverse effects and risk assessment. [23]

Pharmacological knowledge is used to advise pharmacotherapy in medicine and pharmacy.

Drug discovery

Drug discovery is the field of study concerned with creating new drugs. It encompasses the subfields of drug design and development. [24] Drug discovery starts with drug design, which is the inventive process of finding new drugs. [25] In the most basic sense, this involves the design of molecules that are complementary in shape and charge to a given biomolecular target. [26] After a lead compound has been identified through drug discovery, drug development involves bringing the drug to the market. [24] Drug discovery is related to pharmacoeconomics, which is the sub-discipline of health economics that considers the value of drugs [27] [28] Pharmacoeconomics evaluates the cost and benefits of drugs in order to guide optimal healthcare resource allocation. [29] The techniques used for the discovery, formulation, manufacturing and quality control of drugs discovery is studied by pharmaceutical engineering, a branch of engineering. [30] Safety pharmacology specialises in detecting and investigating potential undesirable effects of drugs. [31]

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The drug discovery cycle

Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration; they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMA, and they enforce standards set by the European Pharmacopoeia.

The metabolic stability and the reactivity of a library of candidate drug compounds have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism; one example of a recent computational method is SPORCalc. [32] A slight alteration to the chemical structure of a medicinal compound could alter its medicinal properties, depending on how the alteration relates to the structure of the substrate or receptor site on which it acts: this is called the structural activity relationship (SAR). When a useful activity has been identified, chemists will make many similar compounds called analogues, to try to maximize the desired medicinal effect(s). This can take anywhere from a few years to a decade or more, and is very expensive. [33] One must also determine how safe the medicine is to consume, its stability in the human body and the best form for delivery to the desired organ system, such as tablet or aerosol. After extensive testing, which can take up to six years, the new medicine is ready for marketing and selling. [33]

Because of these long timescales, and because out of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, often costing over 1 billion dollars. To recoup this outlay pharmaceutical companies may do a number of things: [33]

  • Carefully research the demand for their potential new product before spending an outlay of company funds. [33]
  • Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time. [33]

The inverse benefit law describes the relationship between a drugs therapeutic benefits and its marketing.

When designing drugs, the placebo effect must be considered to assess the drug's true therapeutic value.

Drug development uses techniques from medicinal chemistry to chemically design drugs. This overlaps with the biological approach of finding targets and physiological effects.

Wider contexts

Pharmacology can be studied in relation to wider contexts than the physiology of individuals. For example, pharmacoepidemiology concerns the variations of the effects of drugs in or between populations, it is the bridge between clinical pharmacology and epidemiology. [34] [35] Pharmacoenvironmentology or environmental pharmacology is the study of the effects of used pharmaceuticals and personal care products (PPCPs) on the environment after their elimination from the body. [36] Human health and ecology are intimately related so environmental pharmacology studies the environmental effect of drugs and pharmaceuticals and personal care products in the environment. [37]

Drugs may also have ethnocultural importance, so ethnopharmacology studies the ethnic and cultural aspects of pharmacology. [38]

Emerging fields

Photopharmacology is an emerging approach in medicine in which drugs are activated and deactivated with light. The energy of light is used to change for shape and chemical properties of the drug, resulting in different biological activity. [39] This is done to ultimately achieve control when and where drugs are active in a reversible manner, to prevent side effects and pollution of drugs into the environment. [40] [41]

Theory of pharmacology

A trio of dose response curves. Dose response curves are studied extensively in pharmacology. Dose response antagonist.jpg
A trio of dose response curves. Dose response curves are studied extensively in pharmacology.

The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function).

Chemicals can have pharmacologically relevant properties and effects. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic).

Systems, receptors and ligands

The cholinergic synapse. Targets in synapses can be modulated with pharmacological agents. In this case, cholinergics (such as muscarine) and anticholinergics (such as atropine) target receptors; transporter inhibitors (such as hemicholinium) target membrane transport proteins and anticholinesterases (such as sarin) target enzymes. Cholinergic synapse.svg
The cholinergic synapse. Targets in synapses can be modulated with pharmacological agents. In this case, cholinergics (such as muscarine) and anticholinergics (such as atropine) target receptors; transporter inhibitors (such as hemicholinium) target membrane transport proteins and anticholinesterases (such as sarin) target enzymes.

Pharmacology is typically studied with respect to particular systems, for example endogenous neurotransmitter systems. The major systems studied in pharmacology can be categorised by their ligands and include acetylcholine, adrenaline, glutamate, GABA, dopamine, histamine, serotonin, cannabinoid and opioid.

Molecular targets in pharmacology include receptors, enzymes and membrane transport proteins. Enzymes can be targeted with enzyme inhibitors. Receptors are typically categorised based on structure and function. Major receptor types studied in pharmacology include G protein coupled receptors, ligand gated ion channels and receptor tyrosine kinases.

Network pharmacology is a subfield of pharmacology that combines principles from pharmacology, systems biology, and network analysis to study the complex interactions between drugs and targets (e.g., receptors or enzymes etc.) in biological systems. The topology of a biochemical reaction network determines the shape of drug dose-response curve [42] as well as the type of drug-drug interactions, [43] thus can help designing efficient and safe therapeutic strategies. The topology Network pharmacology utilizes computational tools and network analysis algorithms to identify drug targets, predict drug-drug interactions, elucidate signaling pathways, and explore the polypharmacology of drugs.

Pharmacodynamics

Pharmacodynamics is defined as how the body reacts to the drugs. Pharmacodynamics theory often investigates the binding affinity of ligands to their receptors. Ligands can be agonists, partial agonists or antagonists at specific receptors in the body. Agonists bind to receptors and produce a biological response, a partial agonist produces a biological response lower than that of a full agonist, antagonists have affinity for a receptor but do not produce a biological response.

The ability of a ligand to produce a biological response is termed efficacy, in a dose-response profile it is indicated as percentage on the y-axis, where 100% is the maximal efficacy (all receptors are occupied).

Binding affinity is the ability of a ligand to form a ligand-receptor complex either through weak attractive forces (reversible) or covalent bond (irreversible), therefore efficacy is dependent on binding affinity.

Potency of drug is the measure of its effectiveness, EC50 is the drug concentration of a drug that produces an efficacy of 50% and the lower the concentration the higher the potency of the drug therefore EC50 can be used to compare potencies of drugs.

Medication is said to have a narrow or wide therapeutic index, certain safety factor or therapeutic window . This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors.

The effect of drugs can be described with Loewe additivity which is one of several common reference models. [43]

Other models include the Hill equation, Cheng-Prusoff equation and Schild regression.

Pharmacokinetics

Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of drugs. [44]

When describing the pharmacokinetic properties of the chemical that is the active ingredient or active pharmaceutical ingredient (API), pharmacologists are often interested in L-ADME:

Drug metabolism is assessed in pharmacokinetics and is important in drug research and prescribing.

Pharmacokinetics is the movement of the drug in the body, it is usually described as 'what the body does to the drug' the physico-chemical properties of a drug will affect the rate and extent of absorption, extent of distribution, metabolism and elimination. The drug needs to have the appropriate molecular weight, polarity etc. in order to be absorbed, the fraction of a drug the reaches the systemic circulation is termed bioavailability, this is simply a ratio of the peak plasma drug levels after oral administration and the drug concentration after an IV administration(first pass effect is avoided and therefore no amount drug is lost). A drug must be lipophilic (lipid soluble) in order to pass through biological membranes this is true because biological membranes are made up of a lipid bilayer (phospholipids etc.) Once the drug reaches the blood circulation it is then distributed throughout the body and being more concentrated in highly perfused organs.

Administration, drug policy and safety

Drug policy

In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements:

  1. The drug must be found to be effective against the disease for which it is seeking approval (where 'effective' means only that the drug performed better than placebo or competitors in at least two trials).
  2. The drug must meet safety criteria by being subject to animal and controlled human testing.

Gaining FDA approval usually takes several years. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome. [45]

The safety and effectiveness of prescription drugs in the U.S. are regulated by the federal Prescription Drug Marketing Act of 1987.

The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.

Medicare Part D is a prescription drug plan in the U.S.

The Prescription Drug Marketing Act (PDMA) is an act related to drug policy.

Prescription drugs are drugs regulated by legislation.

Societies and education

Societies and administration

The International Union of Basic and Clinical Pharmacology, Federation of European Pharmacological Societies and European Association for Clinical Pharmacology and Therapeutics are organisations representing standardisation and regulation of clinical and scientific pharmacology.

Systems for medical classification of drugs with pharmaceutical codes have been developed. These include the National Drug Code (NDC), administered by Food and Drug Administration.; [46] Drug Identification Number (DIN), administered by Health Canada under the Food and Drugs Act; Hong Kong Drug Registration, administered by the Pharmaceutical Service of the Department of Health (Hong Kong) and National Pharmaceutical Product Index in South Africa. Hierarchical systems have also been developed, including the Anatomical Therapeutic Chemical Classification System (AT, or ATC/DDD), administered by World Health Organization; Generic Product Identifier (GPI), a hierarchical classification number published by MediSpan and SNOMED, C axis. Ingredients of drugs have been categorised by Unique Ingredient Identifier.

Education

The study of pharmacology overlaps with biomedical sciences and is the study of the effects of drugs on living organisms. Pharmacological research can lead to new drug discoveries, and promote a better understanding of human physiology. Students of pharmacology must have a detailed working knowledge of aspects in physiology, pathology, and chemistry. They may also require knowledge of plants as sources of pharmacologically active compounds. [38] Modern pharmacology is interdisciplinary and involves biophysical and computational sciences, and analytical chemistry. A pharmacist needs to be well-equipped with knowledge on pharmacology for application in pharmaceutical research or pharmacy practice in hospitals or commercial organisations selling to customers. Pharmacologists, however, usually work in a laboratory undertaking research or development of new products. Pharmacological research is important in academic research (medical and non-medical), private industrial positions, science writing, scientific patents and law, consultation, biotech and pharmaceutical employment, the alcohol industry, food industry, forensics/law enforcement, public health, and environmental/ecological sciences. Pharmacology is often taught to pharmacy and medicine students as part of a Medical School curriculum.

See also

Related Research Articles

The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes toxicity to the amount that causes the therapeutic effect. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.

Drug tolerance or drug insensitivity is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible and can involve both physiological factors and psychological factors.

<span class="mw-page-title-main">Pharmacodynamics</span> Area of Academic Study

Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs. The effects can include those manifested within animals, microorganisms, or combinations of organisms.

In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.

<span class="mw-page-title-main">Medicinal chemistry</span> Scientific branch of chemistry

Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR).

<span class="mw-page-title-main">Cimetidine</span> Medication

Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.

<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by CYP3A4 gene. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do.

Clinical pharmacology is "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinical pharmacology is inherently a translational discipline underpinned by the basic science of pharmacology, engaged in the experimental and observational study of the disposition and effects of drugs in humans, and committed to the translation of science into evidence-based therapeutics. It has a broad scope, from the discovery of new target molecules to the effects of drug usage in whole populations. The main aim of clinical pharmacology is to generate data for optimum use of drugs and the practice of 'evidence-based medicine'.

A biological target is anything within a living organism to which some other entity is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are proteins and nucleic acids. The definition is context-dependent, and can refer to the biological target of a pharmacologically active drug compound, the receptor target of a hormone, or some other target of an external stimulus. Biological targets are most commonly proteins such as enzymes, ion channels, and receptors.

<span class="mw-page-title-main">Biological half-life</span> Time taken for a drug to halve its concentration in blood plasma

Biological half-life is the time taken for concentration of a biological substance to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma. It is denoted by the abbreviation .

Pharmacotherapy, also known as pharmacological therapy or drug therapy, is defined as medical treatment that utilizes one or more pharmaceutical drugs to improve ongoing symptoms, treat the underlying condition, or act as a prevention for other diseases (prophylaxis).

<span class="mw-page-title-main">Pharmacokinetics</span> Branch of pharmacology

Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific substance after administration. The substances of interest include any chemical xenobiotic such as pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is based on mathematical modeling that places great emphasis on the relationship between drug plasma concentration and the time elapsed since the drug's administration. Pharmacokinetics is the study of how an organism affects the drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.

Safety pharmacology is a branch of pharmacology specialising in detecting and investigating potential undesirable pharmacodynamic effects of new chemical entities (NCEs) on physiological functions in relation to exposure in the therapeutic range and above.

<span class="mw-page-title-main">Deramciclane</span> Drug used to treat anxiety disorders

Deramciclane (EGIS-3886) is a non-benzodiazepine-type anxiolytic drug to treat various types of anxiety disorders. Deramciclane is a unique alternative to current anxiolytics on the market because it has a novel chemical structure and target. It acts as an antagonist at the 5-HT2A receptor, as an inverse agonist at the 5-HT2C receptor, and as a GABA reuptake inhibitor. The two serotonin receptors are G protein-coupled receptors and are two of the main excitatory serotonin receptor types. Their excitation has been implicated in anxiety and mood. Deramciclane does not affect CYP3A4 activity in metabolizing other drugs, but it is a weak inhibitor of CYP2D6. Some studies also show the drug to have moderate affinity to dopamine D2 receptors and low affinity to dopamine receptor D1. Researchers are looking for alternatives to benzodiazepines for anxiolytic use because benzodiazepine drugs have sedative and muscle relaxant side effects.

<span class="mw-page-title-main">Enobosarm</span> Investigational selective androgen receptor modulator

Enobosarm, also formerly known as ostarine and by the developmental code names GTx-024, MK-2866, and S-22, is a selective androgen receptor modulator (SARM) which is under development for the treatment of androgen receptor-positive breast cancer in women and for improvement of body composition in people taking GLP-1 receptor agonists like semaglutide. It was also under development for a variety of other indications, including treatment of cachexia, Duchenne muscular dystrophy, muscle atrophy or sarcopenia, and stress urinary incontinence, but development for all other uses has been discontinued. Enobosarm was evaluated for the treatment of muscle wasting related to cancer in late-stage clinical trials, and the drug improved lean body mass in these trials, but it was not effective in improving muscle strength. As a result, enobosarm was not approved and development for this use was terminated. Enobosarm is taken by mouth.

<span class="mw-page-title-main">Andarine</span> Chemical compound

Andarine is a selective androgen receptor modulator (SARM) which was developed by GTX, Inc for the treatment of conditions such as muscle wasting, osteoporosis, and benign prostatic hypertrophy (BPH), using the nonsteroidal antiandrogen bicalutamide as a lead compound. Development of andarine for all indications has been discontinued, in favor of the structurally related and improved compound enobosarm.

Leon Aarons is an Australian chemist who researches and teaches in the areas of pharmacodynamics and pharmacokinetics. He lives in the United Kingdom and from 1976 has been a professor of pharmacometrics at the University of Manchester. In the interest of promoting the effective development of drugs, the main focus of his work is optimizing pharmacological models, the design of clinical studies, and data analysis and interpretation in the field of population pharmacokinetics. From 1985 to 2010 Aarons was an editor emeritus of the Journal of Pharmacokinetics and Pharmacodynamics and is a former executive editor of the British Journal of Clinical Pharmacology.

Chemical compounds that come as mirror-image pairs are referred to by chemists as chiral or handed molecules. Each twin is called an enantiomer. Drugs that exhibit handedness are referred to as chiral drugs. Chiral drugs that are equimolar (1:1) mixture of enantiomers are called racemic drugs and these are obviously devoid of optical rotation. The most commonly encountered stereogenic unit, that confers chirality to drug molecules are stereogenic center. Stereogenic center can be due to the presence of tetrahedral tetra coordinate atoms (C,N,P) and pyramidal tricoordinate atoms (N,S). The word chiral describes the three-dimensional architecture of the molecule and does not reveal the stereochemical composition. Hence "chiral drug" does not say whether the drug is racemic, single enantiomer or some other combination of stereoisomers. To resolve this issue Joseph Gal introduced a new term called unichiral. Unichiral indicates that the stereochemical composition of a chiral drug is homogenous consisting of a single enantiomer.

Chiral inversion is the process of conversion of one enantiomer of a chiral molecule to its mirror-image version with no other change in the molecule.

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Further reading