2009
DOI: 10.4155/bio.09.128
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Mechanisms of Amine Accumulation in, and Egress from, Lysosomes

Abstract: The human body is continuously exposed to small organic molecules containing one or more basic nitrogen atoms. Many of these are endogenous (i.e., neurotransmitters, polyamines and biogenic amines), while others are exogenously supplied in the form of drugs, foods and pollutants. It is well-known that many amines have a strong propensity to specifically and substantially accumulate in highly acidic intracellular compartments, such as lysosomes, through a mechanism referred to as ion trapping. It is also known … Show more

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Cited by 95 publications
(97 citation statements)
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“…The rapid reversibility of lysosomal trapping of a lipophilic amine is shown by the effects of asphyxiating rats with carbon dioxide, which slightly acidifies the blood and causes a slight decrease in tissue levels and an increase in plasma drug levels (Angus et al, 2008). Although passive diffusion is one mechanism by which lipophilic amines can exit lysosomes, there are other mechanisms by which this can occur, namely mechanisms more relevant for the recycling of phospholipidbound drugs (Goldman et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…The rapid reversibility of lysosomal trapping of a lipophilic amine is shown by the effects of asphyxiating rats with carbon dioxide, which slightly acidifies the blood and causes a slight decrease in tissue levels and an increase in plasma drug levels (Angus et al, 2008). Although passive diffusion is one mechanism by which lipophilic amines can exit lysosomes, there are other mechanisms by which this can occur, namely mechanisms more relevant for the recycling of phospholipidbound drugs (Goldman et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…Antipsychotics can be classifi ed as hydrophobic amine or cationic amphiphile/ amphipath drugs, as they are positively charged by virtue of an amine group that can be protonated, and they display both hydrophilic and hydrophobic properties. It is well recognized that many amines have a strong propensity to specifi cally and substantially accumulate in highly acidic intracellular compartments, such as lysosomes, through a mechanism referred to as ion trapping ( 48 ). In their unionized form, weak basic amines are relatively membrane permeable, but they are membrane impermeable in their ionized conjugate acidic state ( 48 ).…”
mentioning
confidence: 99%
“…It is well recognized that many amines have a strong propensity to specifi cally and substantially accumulate in highly acidic intracellular compartments, such as lysosomes, through a mechanism referred to as ion trapping ( 48 ). In their unionized form, weak basic amines are relatively membrane permeable, but they are membrane impermeable in their ionized conjugate acidic state ( 48 ). Some antipsychotic and antidepressant drugs have been shown to extensively accumulate in lysosomes ( 49,50 ).…”
mentioning
confidence: 99%
“…As such, the prolonged receptor internalisation caused by C26 may provide an additional mechanism of long duration of action at the β 2 adrenoceptor, which may be further exploited by targeting drugs to intracellular compartments e.g. by incorporating physiochemical properties that facilitate ion trapping (Goldman et al, 2009). …”
Section: Discussionmentioning
confidence: 99%