Aluminum is poorly absorbed following either oral or inhalation exposure and is essentially not absorbed dermally. The bioavailability of aluminum is strongly influenced by the aluminum compound and the presence of dietary constituents which can complex with aluminum and enhance or inhibit its absorption. Aluminum binds to various ligands in the blood and distributes to every organ, with highest concentrations found in bone and lung tissues. In living organisms, aluminum is believed to exist in four different forms: as free ions, as low-molecular-weight complexes, as physically bound macromolecular complexes, and as covalently bound macromolecular complexes. Absorbed aluminum is excreted principally in the urine and, to a lesser extent, in the bile, while unabsorbed aluminum is excreted in the faeces. (L739)
The main target organs of aluminum are the central nervous system and bone. Aluminum binds with dietary phosphorus and impairs gastrointestinal absorption of phosphorus. The decreased phosphate body burden results in osteomalacia (softening of the bones due to defective bone mineralization) and rickets. Aluminum's neurotoxicity is believed to involve several mechanisms. Changes in cytoskeletal protein functions as a results of altered phosphorylation, proteolysis, transport, and synthesis are believed to be one cause. Aluminum may induce neurobehavioral effects by affecting permeability of the blood-brain barrier, cholinergic activity, signal transduction pathways, lipid peroxidation, and impair neuronal glutamate nitric oxide-cyclic GMP pathway, as well as interfere with metabolism of essential trace elements because of similar coordination chemistries and consequent competitive interactions. It has been suggested that aluminum's interaction with estrogen receptors increases the expression of estrogen-related genes and thereby contributes to the progression of breast cancer (A235), but studies have not been able to establish a clear link between aluminum and increased risk of breast cancer (A15468). Certain aluminum salts induce immune responses by activating inflammasomes. (L739, A235, A236)
Not listed by IARC. IARC classified aluminum production as carcinogenic to humans (Group 1), but did not implicate aluminum itself as a human carcinogen. (L135) A link between use of aluminum-containing antiperspirants and increased risk of breast cancer has been proposed (A235), but studies have not been able to establish a clear link (A15468).
Aluminum targets the nervous system and causes decreased nervous system performance and is associated with altered function of the blood-brain barrier. The accumulation of aluminum in the body may cause bone or brain diseases. High levels of aluminum have been linked to Alzheimer's disease. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. (L739, L740)
Inhalating aluminum dust causes coughing and abnormal chest X-rays. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. (L739, L740)
申请人：The United States of America as represented by the Secretary of the Army
公开号：US04659708A1
公开（公告）日：1987-04-21
The subject 8-[6-(N-heterocyclic-substituted)hexylamino]-6-methoxy lepidine erivatives have the formula: ##STR1## wherein Z represents methyl or, together with the two contiguous carbon atoms, the benzo moiety of a benzopiperazinyl derivative when Y is --N(R')--, n is an integer from 0 to 2; Y represents --O--, --S--, --S(O)--, --S(O).sub.2 --, and --N(R')--; R' represents hydrogen, alkyl, lower alkyl, R" substituted lower alkyl, cycloalkyl, aryl, sulfonyl, saturated 1,4-diazepinyl, lower alkyl N-cyanocarboximidothioate, or --C(O)R'"; R" represents at least one of hydroxy, alkoxy, aralkoxy, amino, lower alkyl substituted amino, phenyl, halogenated phenyl, or sufonyl; and R'" represents lower alkyl, alkoxy, aralkoxy, amino, lower alkyl substituted amino or aryl substituted amino; and pharmaceutically acceptable salts thereof. These derivatives afford improvement in means for the chemotherapy of leishmaniasis when administered parenterally or orally to infected animals.
Substituted tetrahydrobenzothiazoles as dopaminergic agents
申请人：Warner-Lambert Company
公开号：US04988699A1
公开（公告）日：1991-01-29
Substituted tetrahydrobenzothiazoles are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful as dopamine agonists with selectivity for the presynaptic dopamine receptor and are useful as dopaminergic, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.
Fused benzo compounds containing a nitrogen heterocycle for the
申请人：H. Lundbeck A/S
公开号：US05753661A1
公开（公告）日：1998-05-19
Fused benzo compounds of formula I are provided, wherein A is a 2 to 6 membered hydrocarbon spacer group, B is a polar divalent group selected from a group (a); U is C, N or CH; X is a divalent 3-4 membered chain optionally comprising one or more heteroatoms; R.sup.1 is an aliphatic hydrocarbon group, arylalkyl or diphenylalkyl; R.sup.2 and R.sup.3 are hydrogen or alkyl or together form an ethylene or propylene bridge; R.sup.4, R.sup.5 and R.sup.6 are hydrogen or substituents; R.sup.7 and R.sup.8 are hydrogen or substituents including --COOR.sup.9 and --CONR.sup.10 R.sup.11 ; are 5-HT.sub.1A receptor ligands useful in the treatment of CNS disorders. Pharmaceutical compositions comprising the compounds and their use for the manufacture of a pharmaceutical preparation are also provided.
Compounds of formula I, and their pharmaceutically acceptable salts, ##STR1## in which R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl or alkenyl; or NR.sup.1 R.sup.2 is a heterocyclic group; A is trimethylene optionally substituted by alkyl and the phenyl ring is optionally substituted by substituents such as halogeno, alkenyl, amino, cyano, ureido, alkyl, carbamoylalkyl, alkanoylamino, alkoxycarbonyl, N-alkyl-alkanoylamino, alkanoyl and amines thereof; are inhibitors of squalene synthese and hence useful in treating diseases in which a lowering of cholesterol is desirable. As well as the use of these compounds in medicine, novel compounds, processes for their preparation and pharmaceutical compositions are also referred to.
Fused benzo compounds for the treatment of central nervous system
申请人：H. Lundbeck A/S
公开号：US06140331A1
公开（公告）日：2000-10-31
##STR1## Fused benzo compounds of formula (I), wherein A is a 2 to 6 membered hydrocarbon spacer group, B is a polar divalent group selected from SO, SO.sub.2, and a group (a); U is C, N or CH; X is a divalent 3-4 membered chain optionally comprising one or more heteroatoms; R.sup.1 is an aliphatic hydrocarbon group, arylalkyl or diphenylalkyl; R.sup.2 and R.sup.3 are hydrogen or alkyl or together form an ethylene or propylene bridge; R.sup.4, R.sup.5 and R.sup.6 are hydrogen or substituents; R.sup.7 and R.sup.8 are hydrogen or substituents including, a group --COOR.sup.9 and a group --CONR.sup.10 R.sup.11 ; are 5-HT.sub.1A receptor ligands useful in the treatment of CNS disorders. Pharmaceutical compositions comprising the compounds and their use for the manufacture of a pharmaceutical preparation are also disclosed.
