Clinical pharmacology of the typical classical neuroleptics

Despite the wide differences in the potency of the neuroleptics in current use, and the differences in specificity regarding their effects on various neurotransmitter systems in the mammalian brain, there is little evidence to suggest that their overall efficacy in treating the symptoms of schizophrenia, mania and other psychoses markedly differs. Thus the ''classical'' neuroleptics appear to be effective in attenuating the positive symptoms of schizophrenia (e.g. hallucinations and delusions)...

Neurotransmitters and the pathogenesis of schizophrenia

In its original form, the dopamine hypothesis of schizophrenia postulated that the positive symptoms of the illness arose as a consequence of the Table 11.2. Risk factors for schizophrenia 1. Genetic factors - polygenic inheritance 2. Pre- and perinatal events, e.g. maternal viral infection during second trimester toxaemia and or hypoxia at birth 3. Environmental factors, e.g. the use of cannabis, brain trauma hyperactivity of the dopaminergic system, particularly in the mesocortico-limbic...

Pharmacogenetics and psychopharmacology

For more than 40 years, epidemiological studies have clearly demonstrated a tendency for diseases such as schizophrenia, bipolar disorder and autism to run in families. Thus it has been shown that such disorders are much more frequent in close relatives of patients than in the general population. For example, estimates of the increased risk of suffering from the disorder if the patient has a sibling with the disorder range from nine- to eleven-fold for schizophrenia and about sevenfold for...

Classification of the typical neuroleptics

In addition to their well-established antipsychotic properties, the neuro-leptics have a number of clinically important properties that include their antiemetic and antinauseant actions, their antihistaminic effects and their ability to potentiate the actions of analgesics and general anaesthetics. Reserpine is unique among the neuroleptics in that it is a naturally occurring alkaloid obtained from the snake plant Rauwolfia serpentina. The use of aqueous extracts of the root of this plant for...

D1a

The classical Dj receptor selective antagonists neglected as putative antipsychotics Novel site with low density, corticolimbic localization no specific function(s) or selective antagonist yet known The classical D2 isomorphs reliable correlation between D2 affinity and neuroleptic potency Novel site with low density, corticolimbic localization no specific function(s) or selective antagonist yet known Novel site with low density, corticolimbic localization no specific function(s) or selective...

Pseudodementia

This is defined as any condition which mimics dementia. The commonest psychiatric disorder which mimics dementia is depression in which the retardation can be confused with the apathy of dementia. The guiding principle is careful clinical assessment and, if in doubt, a trial of an appropriate antidepressant. GERIATRIC PSYCHOPHARMACOLOGY Depression A disturbance in the sleep pattern is a common symptom of depression but changes in the sleep pattern also occur as a consequence of ageing. Once...

Relationship between plasma antidepressant concentrations and the therapeutic response

Over the past 20 years there has been widespread interest in monitoring plasma antidepressant, particularly tricyclic, levels to optimize the response to treatment. One aspect of this research that is universally agreed upon concerns the extensive interindividual variability among patients, but it is still uncertain whether a knowledge of the plasma drug concentration is of clinical value. For the tricyclic antidepressants (TCAs) the two major oxidative pathways that occur in the liver are...

Functional Neuroanatomy of the Brain

Understanding the relationship between brain structure and function, and particularly how this relationship becomes disturbed in the mentally ill, is one of the major challenges to clinical and experimental neuroscientists. The brain may be described in terms of its general structure and key anatomical areas. It may also be described in terms of the cellular or subcellular structure of the different types of cells that constitute the brain. Finally it may be considered in terms of its...

Drugs used in Parkinsons disease

The discovery that dopamine was depleted in the basal ganglia of patients who suffered from Parkinsonism at the time of death led to the rational development of the therapeutic treatment, namely the use of L-dopa. Since dopamine does not cross the blood-brain barrier, and is rapidly catabolized in the wall of the intestinal tract by monoamine oxidase (MAO) the amine itself cannot be administered. However, L-dopa is rapidly decarboxylated in the brain to dopamine and it was found that high doses...

The biochemical basis of important drug interactions

The biotransformation of a drug may either lead to the termination of its pharmacological activity or, occasionally, to its activation to a pharmacologically effective entity. It is also possible that a drug may be metabolized to form pharmacologically or toxicologically active metabolites. Whatever the outcome, the biotransformation of a drug ultimately involves its conversion to a more hydrophilic form thereby facilitating its excretion into the urine. However, some lipophilic drugs and their...

Cannabis and the cannabinoids

The hemp plant, Cannabis sativa, has been known for its commercial use as a source of hemp for the manufacture of rope, sacking and so on for well over 2000 years. The hemp seeds have also been used as a source of oil, as an animal feed and as a form of soap, while the leaves were first used in China because of the psychoactive ingredients they contained. From China, the use of hemp spread first to India and then to Europe via the Middle East in the 16th century. All parts of the hemp plant...

Biochemical pathways leading to the synthesis and metabolism of the major neurotransmitters in the mammalian brain

No attempt will be made to give an overview of the main pathways of the several dozen neurotransmitters, neuromodulators and co-transmitters which are possibly involved in the aetiology of mental illness. Instead a summary is given of the relevant pathways involved in the synthesis and metabolism of those transmitters which have conventionally been considered to be involved in the major psychiatric and neurological diseases and through which the psychotropic drugs used in the treatment of such...

Some Important Psychotropic Drug Interactions

Tricyclic antidepressants + fluoxetine, paroxetine or sertraline increased pharmacological and toxicological effects of the tricyclic due to decreased hepatic metabolism. This is a potentially hazardous combination. Tricyclic antidepressants + MAOIs stroke, hyperpyrexia and convulsions can occur. Potentially a hazardous combination. Tricyclic antidepressants + directly acting sympathomimetic amines (e.g. noradrenaline, adrenaline) hypertension and arrhythmias due to enhancement of the...

Gaba

Increased density of D2 receptors Increased cortical DA innervation Increased D4-like receptor binding Alterations in D3 receptor binding Decreased presynaptic markers Decreased HC AMPA and kainate receptor expression Minor changes in FC NMDA R sub-units Altered glutamate fibres in cingulate cortex Decreased FC 5-HT2a receptor expression Increased FC 5-HT1A receptors Increased 5-HT transporter affinity Developmental and trophic roles of 5-HT Increased density of FC GABAergic terminals Increased...

Summary of the pharmacological properties of antidepressants in general use in Europe

Sertraline Muscarinic

This group of drugs was introduced during the early 1960s following the chance discovery of the antidepressant effects of imipramine. The therapeutic efficacy of the TCAs has been ascribed to their ability to inhibit the reuptake of noradrenaline and serotonin into the neuron following the release of these transmitters into the synaptic cleft. In addition, these drugs inhibit the muscarinic receptors (causing dry mouth, impaired vision, tachycardia, difficulty in micturition), histamine type-1...

Psychotropic Drug Structure

Amantadine Parkinson

Relationship between the efficacy of L-dopa treatment and time. It should be noted that patients who fail to show any improvement (< 50 ) after short-term (< 1 year) treatment with L-dopa are probably not suffering from idiopathic Non-specific MAO inhibitors such as phenelzine, isocarboxazid or tranylcypromine are contraindicated in patients on L-dopa therapy as they are likely to precipitate hyperpyrexia and hypertension. However, recently the selective MAO-B inhibitor...

The psychostimulants cocaine and the amphetamines

Cocaine is a major alkaloidal component from the Andean bush Erythroxylon coca. Leaves of this plant are chewed by Andean Indians to decrease the feeling of hunger and fatigue there is little evidence that dependence is caused by this means of administration. A major health problem arises, however, when cocaine is used in industrialized countries. Thus in the US over 20 million people are estimated to use the drug, by nasal administration (snorting), injection of the salts, or smoking the free...

Neurochemical changes associated with Alzheimers disease

Scan Extrapyramidal Tracts

The pathological lesions seen in the brain of those with AD are inevitably associated with dysfunctions of the neurotransmitter systems. Of these, deficits in the neocortical cholinergic system have been well established for over a decade but more recently changes in the concentrations of the neuropeptides somatostatin and corticotrophin releasing factor (CRF) have been added to the list. Deficits in the biogenic amines noradrenaline and serotonin have also been reported to occur but a...

O Z

Summary of the site of action of mirtazepine (NaSSA). The inhibitory a2 adrenoceptors facilitate the release of both noradrenaline and serotonin (via the heteroceptor on the 5-HT neuron). This is further enhanced by the aj receptor on the serotonin cell body. Thus mirtazepine (and to a lesser extent mianserin) enhance both noradrenergic and serotonergic Herbal antidepressants - St John's Wort (Hypericum officinalis) St John's Wort in recent years has become widely used in Europe and...

Generic and Proprietary Names of Some Common Psychotropic Drugs

This list of drugs is not intended to be entirely comprehensive and in most cases only the most frequently used proprietary names are given. For detailed coverage of the area the reader is referred to a local pharmacopoeia. Our best efforts to ensure accuracy have been made. The publisher bears no responsibility for inaccuracy. European (mainly Irish UK) trade name Concilium Madopar (with L-dopa) Artane Cogentin Akineton Lexotan Parlodel Elaril Endep Asendin Benzedrine Auralgan European (mainly...

Serotonin and its role in depression

Serotonin is believed to play a multifunctional role in depression which is to be anticipated from its involvement in the physiological processes of sleep, mood, vigilance, feeding and possibly sexual behaviour and learning, all of which are deranged to varying extents in severe depression. However, the involvement of precise serotonin receptor subtypes in depression, and in the action of antidepressants, is still far from clear. One approach to unravelling the changes in serotonin receptors in...

Relationship between plasma anxiolytic concentrations and the therapeutic response

While the individual drugs in the benzodiazepine group differ in potency, all benzodiazepines in common use have anxiolytic, sedative-hypnotic, anticonvulsant and muscle-relaxant activity in ascending order of dose. The main clinical difference between the individual drugs lies in the time of onset of their therapeutic effect, and the intensity and duration of their clinical activity. All benzodiazepines are derived from weak organic acids and some, such as midazolam, form water-soluble salts...

Novel antipsychotics in development

Serotonin receptor antagonists as antipsychotics The improvement of the secondary negative symptoms, and the symptoms of depression often associated with schizophrenia, has been an important feature of the atypical antipsychotics. Such pharmacological features may reside in the actions of the atypical antipsychotics on 5-HT2 receptors in addition to their actions on dopamine receptors. For example, all these drugs have a high affinity for 5-HT2A and 2C receptors, and to a lesser extent 5-HT6...

Aspects of the biochemical basis of depression

Research into the chemical pathology of depression has mainly concentrated on four major areas 1. Changes in biogenic amine neurotransmitters in post-mortem brains from suicide victims. 2. Changes in cerebrospinal fluid (CSF) concentrations of amine metabolites from patients with depression. 3. Endocrine disturbances which appear to be coincidentally related to the onset of the illness. 4. Changes in neurotransmitter receptor function and density on platelets and lymphocytes from patients...

Enantiomers their importance in psychopharmacology Introduction

The majority of naturally occurring drugs and biologically active compounds are asymmetrical in their chemical structure. This means that the molecule is structured around one or more carbon atoms in such a way that the molecule is distributed mostly on the right (R rectus) or left (S sinister) of the symmetrical carbon atom, the so-called chiral centre of the molecule. Thus a large proportion of psychotropic drugs in current use possess one or more chiral centres and therefore exist in pairs...

Classification of neurotransmitter receptors

Muscarinic Receptor Camp

The British physiologist Langley, in 1905, was first to postulate that most drugs, hormones and transmitters produce their effects by interacting with specific sites on the cell membrane which we now call receptors. Langley's postulate was based on his observation that drugs can mimic both the specificity and potency of endogenous hormones and neurotransmitters, while others appear to be able to selectively antagonize the actions of such substances. Thus, substances which stimulate the...

The Interrelationship Between Psychopharmacology and Psychoneuroimmunology

The adverse effects of stress and depression, the effects of bereavement, unemployment and social isolation on mental and physical health have been known since antiquity. Aristotle advised physicians, ''Just as you ought not to attempt to cure eyes without head or head without body, so you should not treat body without soul.'' One of the fathers of modern medicine put it more scientifically in the 19th century when he recommended that when attempting to predict health outcomes from tuberculosis...

Glossary of some Common Terms Used in Psychopharmacology

This glossary should be used in conjunction with the index. Action potential Addiction Adenylate cyclase Use of a legal or illicit substance or medication for non-medical or pleasurable purposes unconnected with medically approved indications. Capacity of a drug to produce physiological or psychological dependence and alter the behaviour in a manner detrimental to the individual. Refers to ability to acetylate organic compounds in the liver. A rapid acetylator refers to an individual whose...

Historical development of antidepressants

The use of cocaine, extracted in a crude form from the leaves of the Andean coca plant, has been used for centuries in South America to alleviate fatigue and elevate the mood. It was only relatively recently, however, that the same pharmacological effect was discovered when the amphetamines were introduced into Western medicine as anorexiants with stimulant properties. Opiates, generally as a galenical mixture, were also widely used for centuries for their mood-elevating effects throughout the...

Potential cardiotoxicity of antipsychotic drugs

Most antipsychotic drugs have effects on the heart as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indication notice and the atypical antipsychotic sertindole had its licence withdrawn because of concerns about its potential cardiotoxicity. It has been known since the 1960s that ECG abnormalities are relatively common in those patients on antipsychotics, occurring in approximately 25 of all cases. The most commonly reported changes...

Nipecotic Acid

Folic Acid Psychotropic Drugs Decrease

Clozapine Amoxapine Clomipramine Amitriptyline of nipecotic acid, guvacine which also have anticonvulsant activity at least in experimental animals. However, the major development in the pharmacology of the GABAergic system has been in drugs which facilitate the functioning of the GABA-A receptors. These will be discussed later. There are three types of GABA receptor, A, B and C. Unlike the ionotropic GABA-A receptors, the GABA-B receptors are metabotropic and coupled via inhibitory G-proteins...

L

Main function of brain areas shown Amygdala - An anatomically coherent subsystem within the basal forebrain. Verbal and non-verbal expressions of fear and anger are interpreted by the amygdala. Cerebellum - One of the seven parts of the brain that is responsible for muscle co-ordination and modulation of the force and range of movement. It is involved in the learning of motor skills. Cortex - The most highly developed area in humans and divided into four main regions, namely...