Central nervous system major groups

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... 

The treatment of bacterial infections of the central nervous system highlights a number of important therapeutic considerations. Bacterial meningitis is caused by a variety of bacteria although their incidence varies with age. In the neonate, E. coli and group B streptococci account for the majority of infections, while in the preschool child H. influenzae is the commonest pathogen. Neisseria meningitidis has a... 

The billions of individual neurones within the nervous system communicate with each other and with the target tissues via chemical neurotransmitters. There is a bewildering array of chemicals which act as neurotransmitters or neuromodulators in peripheral or central nervous systems. These compounds fall into four major groups and some examples are shown in Table 4.3. 

Sulfonamides can be divided into three major groups (1) oral, absorbable (2) oral, nonabsorbable and (3) topical. The oral, absorbable sulfonamides can be classified as short-, intermediate-, or long-acting on the basis of their half-lives (Table 46-1). They are absorbed from the stomach and small intestine and distributed widely to tissues and body fluids (including the central nervous system and cerebrospinal fluid), placenta, and fetus. Protein binding varies from 20% to over 90%. Therapeutic concentrations are in the range of 40-100 mcg/mL of blood. Blood levels generally peak 2-6 hours after oral administration. 

All agonists in this therapeutic group decrease the sensation of painful stimuli, which is their main clinical application. They tend to subdue dull, persistent pain rather than sharp pain, but this difference is to some extent dose dependent. The major difference between the non-opioid analgesics such as aspirin and the opiates is that the former reduce the perception of peripherally mediated pain, by reducing the synthesis of local hormones that activate the pain fibres, whereas the latter attenuate the affective reaction to pain without affecting the perception of pain. This clearly suggests that the site of action of the opiate analgesics is in the central nervous system. 

The 3-aminomethyl-l-pyrrolidinyl radical, which was considered to be bioiso-steric to piperazine [91], also produced highly active quinolones, which were however also found not to be tolerated. In trovafloxacin 16 [92], the 3-aminomethyl-l-pyrrolidinyl radical is integrated into a bicydic amine structural unit with a free amino group [(la,5a,6a)-6-amino-3-azabicyclo[3.1.0]hexane]. A correlation probably exists between the increased central nervous system (CNS) side effects obtained with this quinolone [93] and the 2,4-difluorophenyl radical in the 1-posi-tion. Severe hepatic intolerance reactions finally resulted in major restrictions on its use, which was then limited in the USA to severe clinical infections [68]. 

Haloaldehydes and haloketones have received very little attention. Members of this class have been identified as key metabolites of chemicals such as TCE, vinyl chloride, and dibromochloropropane. Trichloroacetaldehyde and chloral hydrate are important compounds of this group. Chloral hydrate is primarily known for its depressant effects on the central nervous system and doses of 500-2000 mg produce central nervous system depression in humans. It is also known to cause liver damage. This compound is classified as group 3 by lARC. TCA and DCA are major metabolites of chloral hydrate. 

Medication stimulates the central nervous system to induce a therapeutic response. There are four major groups of medication that stimulate the central nervous system. They are ... 

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