THA increases action potential duration of central histamine neurons in vitro.
Long-term administration of 9-amino-1,2,3,4-tetrahydroacridine (THA) has been reported to produce marked clinical improvement in patients suffering from Alzheimer's disease. The dramatic enhancement of cognitive function seen with THA contrasts sharply with the modest improvements seen with other forms of anticholinesterase therapy, suggesting that additional mechanisms might play a role in its therapeutic efficacy. When applied to hypothalamic histamine neurons maintained in vitro, THA produced a dose-dependent increase in action potential duration. By its effect upon action potential duration, THA may increase release of transmitter from the axon terminals of cortically projecting aminergic neurons which have been shown to degenerate in Alzheimer's disease. Thus, the therapeutic efficacy of THA may derive from a combination of its anticholinesterase activity and its effects upon the duration of action potentials of aminergic neurons.
Reiner
P B
PB
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
McGeer
E G
EG
D000109:Acetylcholine / Q000502:physiology; D000200:Action Potentials / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000609:Aminoacridines / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008326:Mammillary Bodies / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology*
D000609:Aminoacridines; D002800:Cholinesterase Inhibitors; D012701:Serotonin; D013619:Tacrine; D006632:Histamine; D000109:Acetylcholine; D009638:Norepinephrine