Central nervous system differences

A hydrogen bond, involving an acidic hydrogen atom borne by a fluorine-substituted or halogen-substituted carbon, seems to contribute to the activity and selectivity of volatile fluorinated anesthetics (Table 3.2). These molecules, although nonfunctional, can bind stereoselectively with protein targets of the central nervous system. Different biological behaviors have been reported for both enantiomers of isoflurane (cf. Chapter 8). ... 

Pani L, Kuzmin A, Diana M, et al Calcium receptor antagonists modify cocaine effects in the central nervous system differently. Eur J Pharmacol 190 217-221, 1990... 

Taste-active chemicals react with receptors on the surface of sensory cells in the papillae causing electrical depolarization, ie, drop in the voltage across the sensory cell membrane. The collection of biochemical events that are involved in this process is called transduction (15,16). Not all the chemical steps involved in transduction are known however, it is clear that different transduction mechanisms are involved in different taste quaUties different transduction mechanisms exist for the same chemical in different species (15). Thus the specificity of chemosensory processes, ie, taste and smell, to different chemicals is caused by differences in the sensory cell membrane, the transduction mechanisms, and the central nervous system (14). 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

Research for an antidepressant among non-tricyclic compounds with pharmacological effects qualitatively different from those of the conventional tricyclic compounds led to the preparation and testing of a series of indazole derivatives for reserpine-like activity in mice. l-[3-(Dimethylamino)propyl]-5-methyl-3-phenyl-l//-indazole (FS-32 692) antagonizes reserpine-induced effects and potentiates amphetamine-induced self-stimulation and l-Dopa-induced increase in motor activity. FS-32 produces an anticholinergic action mainly on the central nervous System, while the action of imipramine occurs centrally as well as peripherally (79AF511). 

Cocaine. This lias a bitter taste, is mydriatic, produces local anaesthesia and is toxic. After absorption, or when taken internally, it acts chiefly by stimulation of the central nervous system, succeeded by depression. Since the two phases may be present in different areas simultaneously, a mixed result may ensue. With large doses the chief symptoms are those of medullary depression. Death is due to paralysis of the respiratory centre. The main use of cocaine in medicine is as a local anaesthetic. 

According to Biberfeld, palmatine, calumbamine and jatrorrhizine all paralyse the central nervous system in frogs palmatine also produces this effect in mammals and differs from the other two in stopping respiration, probably by paralysis of the respiratory centre. All three alkaloids lower the blood pressure on intravenous injection, palmatine being the most active. 

Several splice variants of MOP (formerly MOR-1) have been cloned (MOP-1A to MOR-1X). The B, C, andD variants differ in their amino acid sequence at the C-terminal end [4]. These receptor valiants differ in their distribution in the central nervous system and in the rate of internalization and desensitization upon... 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

The present chapter will address the following issues (1) a very brief overview on the properties of the different types of Cl -channels in the various mammalian cells (2) a short summary on what is known of Cl channels on a molecular basis (3) a discussion of pharmacological agents blocking the various Cl -channels and (4) a specific section dealing with the regulation of epithelial and maybe other Cl -channels. This entire area has been reviewed rather extensively in the recent past. A large number of references will be provided in order to keep this text concise. The entire field of Cl -channels in the central nervous system will only be touched upon to compare these channels to the Cl -channels in apolar cells and epithelia. 

Kelder et al. [19] have shown that PSA can be used to model oral absorption and brain penetration of drugs that are transported by the transcellular route. A good correlation was found between brain penetration and PSA (n=45, r=0.917). From analyzing a set of 2366 central nervous system (CNS) and non-CNS oral drugs that have reached at least phase 11 clinical trials it was concluded that orally active drugs that are transported passively by the transcellular route should have PSA< 120 Al In addition, different PSA distributions were found for CNS and non-CNS drugs. 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

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