Drug development neurotransmitter systems

These approaches to receptor identification and classification were, of course, pioneered by studies with peripheral systems and isolated tissues. They are more difficult to apply to the CNS, especially in in vivo experiments, where responses depend on a complex set of interacting systems and the actual drug concentration at the receptors of interest is rarely known. However, the development of in vitro preparations (acute brain slices, organotypic brain slice cultures, tissue-cultured neurons and acutely dissociated neuronal and glial cell preparations) has allowed more quantitative pharmacological techniques to be applied to the action of drugs at neurotransmitter receptors while the development of new recording methods such as patch-clamp... 

Substance P, an undecapeptide, is abundant both in the periphery and in the central nervous system. It is usually co-localized with one of the classical neurotransmitters, most commonly serotonin. Substance P is thought to have a role in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety. The substance-P-preferring receptor neurokinin-1 has been focused on most intensively in drug development, and existing... 

Peptide hormones and neurotransmitters are primary agents of communication between different cell types In the body of complex living systems Including man. Thus, analogs of natural peptide hormones and neurotransmitters with appropriate properties have exceptional potential as drugs. Despite this potential and the need for peptide drugs, development has been slow. Why ... 

Information processing in the human brain via neuro-chemically defined neuronal systems is complex. Therefore, it remains a challenge to conceptualize psychiatric disorders and their treatment in a reductionistic framework of chemical neuroanatomy. We can nonetheless broadly state that the anatomic organization of neurotransmitter systems determines their behavioral affiliation, and that receptors modulate the electrical or biochemical properties of neurons, with direct relevance to the mechanism of action of psychotropic drugs. Future research will provide more detailed information on the subtypes of neurons and specific neurotransmitters systems that are abnormal in psychiatric disorders, and provide a more rational approach to the development of new treatment interventions. 

With the rapid ongoing developments in neuroscience, we are likely to see further reliance on drug probes to test the functional integrity of neurotransmitter systems in specific disorders. An ever-increasing number of biochemical processes are being elucidated that may mediate a specific psychotropic s effects, including ... 

In the hope of developing either a more effective agent or one with fewer adverse effects, medicinal chemists have synthesized a number of new compounds. Preclinical animal model studies are used to select potentially useful drugs, using a profile of pharmacological properties reflecting differential blockade of dopamine, as well as other neurotransmitter systems (e.g., 5-HT). This research has led to the development of several new classes, as noted earlier in this chapter. 

Stahl s Essential Psychopharmacology has established itself as the preeminent source of education and information in its field. This much expanded second edition enlists advances in neurobiology and recent clinical developments to explain with renewed clarity the concepts underlying drug treatment of psychiatric disorders. New neurotransmitter systems, new theories of schizophrenia, clinical advances in antipsychotic and antidepressant therapy, new coverage of attention deficit disorder, sleep disorders, and drug abuse, and a new chapter on sex-specific and sexual function-related psychopharmacology—these are all features of this edition. 

More than a dozen drugs, almost all of them in use for many years, can be classified as neuroleptics. The phenothiazine derivatives were originally the most commonly used class of neuroleptic drugs. Chlorproma-zine is the prototype, developed in France and introduced into North America in 1953 by Heinz Lehmann. Its brand name in Canada and England is Largactil, and in the United tates, Thorazine. The antidepressant amoxapine (Asendin) is metabolized into a neuroleptic and has similar effects and, more important, adverse effects, such as tardive dyskinesia. All the classic neuroleptics block dopamine, but all of them also affect other neurotransmitter systems. 

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