Central nervous system drugs antipsychotics

Further chemical modification of the phenylpiperidine moiety has proven unusually fruitful in producing medicinal agents that affect the central nervous system. First, a series of compounds loosely related to the reversed meperidines produced several drugs with important antipsychotic activity. Further discussion of this pharmacologic activity, often referred to as major tranquilizer activity, will be found in the section on phenothiazines. The group led by Janssen took advantage of the chemistry of the... 

Antipsychotic drugs have profound effects on multiple central nervous system receptors, and these effects are compounded when... 

Dopamine is the immediate precursor in the synthesis of norepinephrine (see Figure 6-5). Its cardiovascular effects were described above. Endogenous dopamine may have more important effects in regulating sodium excretion and renal function. It is an important neurotransmitter in the central nervous system and is involved in the reward stimulus relevant to addiction. Its deficiency in the basal ganglia leads to Parkinson s disease, which is treated with its precursor levodopa. Dopamine receptors are also targets for antipsychotic drugs. 

In the central nervous system, there are close associations between NT and dopamine systems, and NT may be involved in clinical disorders involving dopamine pathways such as schizophrenia, Parkinson s disease, and drug abuse. Consistent with this, it has been shown that central administration of NT produces effects in rodents similar to those produced by antipsychotic drugs. 

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

Tertiary-amine muscarinic receptor antagonists gain access to the central nervous system and are therefore the anticholinergic drugs used to treat parkinsonism and the extrapyramidal side effects of antipsychotic drugs. Specific agents used primarily for these conditions include benztropine mesylate (Cogentin) and trihexyphenidyl hydrochloride (Artane, others). 

The tertiary members of these classes (Figure 8-2) are often used for their effects on the eye or the central nervous system. Many antihistaminic (see Chapter 16 Histamine, Serotonin, the Ergot Alkaloids), antipsychotic (see Chapter 29 Antipsychotic Agents Lithium), and antidepressant (see Chapter 30 Antidepressant Agents) drugs have similar structures and, predictably, significant antimuscarinic effects. 

Katzung PHARMACOLOGY, 9e > Section V. Drugs That Act in the Central Nervous System > Chapter 29, Antipsychotic Agents Lithium > ... 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

MAO inhibitors will act peripherally and may act centrally, again depending on their pharmacokinetic properties. They have, like reserpine, been used for both antihypertensive and antipsychotic treatment but now been superseded by more selectively acting drugs. However, there recently has been renewed interest in the development of MAO B-selec-tive inhibitors, since that enzyme subtype acts preferentially on serotonin and in the central nervous system some of the side effects could thus be avoided or ameliorated. MAO B inhibitors have also been reported to increase the lifetime of dopamine and therefore to be beneficial in Parkinson s disease similarly, inhibitors of COMT have more recently been introduced as a supplement to therapy in this disease. 

Also note that the potential for an interaction between drugs does not preclude their concurrent use. Certain combinations are routinely prescribed without problems in many patients (as with lithium and antipsychotics), whereas others are contraindicated due to the severity of the interaction (for example, MAOIs and SSRIs). However, whenever psychiatric medications are coadministered, the additive potential of central nervous system depression and anticholinergic effects must be considered. 

Neuroleptic. A drug producing symptoms similar to those of depressant diseases of the central nervous system (CNS). Frequently used to refer to an antipsychotic agent. 

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