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Chapter 2

Chapter 2 - Drugs and the Brain.docx

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Chapter 2: Drug Classification and behavioral Assessment o Drugs with almost identical molecular structures may induce entirely different effects, while other drugs whose molecular structures are quite different may induce almost identical effects o One drug might have one effect at one dose and entirely different effect at another o A drug may have multiple psychological effects in a certain dose range, and depending on the population taking it, some of these effects may be viewed as desirable in one person and undesirable in another o It is common in psychopharmacology to describe a drug as belonging to a particular class or type based upon the psychological effect produced or the desired therapeutic action  There are some advantages to using such a classification system. Conveys some meaning about the effects of the new drug. o Drugs that are class as “major psychomotor stimulants” share a set of properties, including actions such as enhancing attention and increasing various types of motor activities o Drugs that are class as “antipsychotic” blunt the florid symptoms of schizophrenia and also are useful for treating mania  Many drugs that are classed as sedative-hypnotics induce stimulant-like effects or behavioral disinhibition at low doses o In clinical practice, “antidepressants” are sometimes used to treat anxiety, while “anxiolytics” can be used to treat depression  There are drugs that are labels as “atypical: because they show an unusual preclinical or clinical profile; clozapine is considered an atypical antipsychotic, and buspirone is classed as an atypical anxiolytic o There are some drugs that defy categorization because they exert actions that cross several categories, but do not fit easily into any one category  Example: delta-9-tetrahydrocannabinol has some of the properties of a sedative-hypnotic, a stimulant, and a mild hallucinogen, but does not fit squarely into any of these classes  MDMA (Ecstasy) has some properties of stimulants and hallucinogens, but some researchers have argued that it should not be put in either category, and instead would merit membership in a newer category (ectactogen) o In humans, the therapeutic effects of drugs often are assessed by rating scales that attempt to measure the symptoms of a particular disorder; example Hamilton Depression Rating Scale or Beck Depression Inventory can be used to assess the effects of antidepressant drugs, while the Hamilton Anxiety Scale is used to measure anxiolytic effects of drugs  Similarly, the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale are used to measure the therapeutic effects of antipsychotic drugs o There are a wide variety of animal tests that also are used to assess the effects of drugs  These tests can be used to determine if a drug has a particular set of properties, or if the drug has a likelihood of showing a particular side effect  Examples of behavioral tests in animals that are used to assess the effects of drugs include: a. Open field locomotion – stimulants – increases locomotor activity b. Operant response rate – stimulants – increase rate on schedules of reinforcement generating low rates c. Rotarod – sedative/hypnotics – induce ataxia or incoordination d. Elevated plus maze – anxiolytics – increase entry to or time spent in open arms e. Radial arm maze – cognitive – enhance spatial working memory f. Morris Water maze – enhancers – reverse effect of a drug or lesion that impairs memory  In addition, animal models are used in the process of drug development. For example, a test such as the elevated plus maze is one of the standard preclinical tests in rodents for assessing potential anxiolytic effects of a drug  Drugs often are assessed for abuse liability by tests of self-administration o The elevated plus maze, preclinical test of potential anxiolytic (antianxiety) effects in rodents  Rodents normally avoid open spaces, such as the open arms, and prefer to be in the closed arms, which have solid walls and are shaded.  Increases in the number of entries into or time spent in the open arms, as opposed to the closed arms, can be used to predict anxiolytic effects in humans  Several common anxiolytic drugs, such as Valium or Xanax, produce this effect o One can describe drugs in terms of their direct neurochemical actions. The ability of a drug to induce a behavioral effect is dependent upon its ability to alter the process of chemical transmission in the nervous system  The action of a drug can be described as the intersection of the transmission process being affected and the neurotransmitter/neuromodulator being affected  For example, a drug can be said to increase dopamine synthesis or block serotonin storage.  Some other psychomotor stimulants act to stimulate the release of dopamine and norepinephrine. Virtually all antipsychotic drugs currently used block dopamine receptors, while minor stimulant caffeine antagonizes adenosine receptors o Initially, when a pharmaceutical company discovers or synthesizes a promising new drug, it is given a code name, generally consisting of two or more letters and a series of numbers  Chemical name provides a complete description of a particular molecule according to specific rules of organic chemistry  Generic name of the compound indicates its legal, official, or nonproprietary name, which is typically the official name cited in research reports on the drug
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