Back to Ketotifen, part antihistamine part mast cell stabilizer ... It's one that initially can cause drowsiness but the affect wears off. I would assume if the drowsiness indicates crossing the BBB that it should continue to cause drowsiness?
The initial week of daytime drowsiness on Ketotifen is long gone, but I do find it helps my sleep a lot (possibly by lowering excess histamine in my brain), which is crucial, since I've had about seven years straight of significant sleep issues. I also have much better daytime energy. So this may be a risk/reward thing and of course don't take more than one needs. I keep coming back to that I haven't had time to research histamine in the brain, which has got to be a very complex picture with goods and bads and balances and no way to know empirically what's going on in there, with or without antihistamines? When do we know that a person has too much histamine detrimentally affecting their brain which overrides anticholinergic concerns up to the lowest effective dose?
(The above is currently modified by the fact that spring pollens are knocking me off course again and I'm not getting enough meds to deal with that too.)
Also my doc wants me on an H2 blocker as well and recommends Zantac, standard recommendation for mast cell issues. I'm cautious to add another possible anticholinergic; however, I find this, rather old from 2000:Blockade of histamine H2 receptors attenuate blood-brain barrier permeability, cerebral blood flow disturbances, edema formation and cell reactions following hyperthermic brain injury in the rat.
Role of histamine H2 receptors in blood-brain barrier (BBB) disturbances, cerebral blood flow (CBF), brain edema formation, and cell injury caused by heat stress in a rat model was examined using the pharmacological approach. Blockade of histamine H2 receptors by cimetidine or ranitidine significantly attenuated the BBB permeability to Evans blue albumin and I-sodium extravasation, brain edema formation and cell injury
following 4 h heat stress in rats at 38 degrees C. These drug treatments also restored the CBF to near normal values. These beneficial effects in heat stress were most marked in rats treated with ranitidine compared to cimetidine
given in identical dosage. Our observations suggest that blockade of histamine H2 receptor is beneficial in hyperthermic brain injury and indicates that histamine is involved in the pathophysiology of heat stress induced brain dysfunction. Our study strongly suggests further need to develop more specific and sensitive histaminergic H2 receptor blockers for the treatment of neurological ailments.
" http://www.ncbi.nlm.nih.gov/pubmed/1145 ... $=activity
Now last I checked I'm not a rat (I'll triple check that later,) and I'm not sure if this is comparable, but I have low heat tolerance, and my mind goes mushy when I get too hot, which is before others do... "histamine is involved in the pathophysiology of heat stress induced brain dysfunction".
Another question I'd have is whether high histamine levels in the brain have some direct affect on the cholinergic pathways. Maybe they are procholinergic so some anticholinergic effect in the brain could be desirable in some?
So I think this issue of histamine and H1/H2 blockers may be very complex when it comes to the brain?
Then there's this, 2013:
Am J Alzheimers Dis Other Demen. 2013 Jun;28(4):327-36. doi: 10.1177/1533317513488925. Epub 2013 May 15.
The neglected role of histamine in Alzheimer's disease.
Naddafi F1, Mirshafiey A.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques accumulation and cognitive impairment. Both environmental factors and heritable predisposition have a role in AD. Histamine is a biogenic monoamine that plays a role in several physiological functions, including induction of inflammatory reactions, wound healing, and regeneration. The Histamine mediates its functions via its 4 G-protein-coupled Histamine H1 receptor (H1R) to histamine H1 receptor (H4R). The histaminergic system has a role in the treatment of brain disorders by the development of histamine receptor agonists, antagonists. The H1R and H4R are responsible for allergic inflammation. But recent studies show that histamine antagonists against H3R and regulation of H2R can be more efficient in AD therapy.
In this review, we focus on the role of histamine and its receptors in the treatment of AD, and we hope that histamine could be an effective therapeutic factor in the treatment of AD.
I believe there's more out there on the topic, but that's all I have time for now.
I think I'll try the Zantac on the theory that I am more in need of H2 blockade than avoiding a 1 point anticholinergic ("low risk of anticholinergic side effects").
ApoE 3/4 > Thanks in advance for any responses made to my posts.