I take etodolac, which reduces COX-2 (and also, some COX-1, so I take misoprostol with it.) It works great for osteoarthritis. Anyone else on a COX-2 inhibitor?

Neuroscience

PNAS | April 29, 2003 | vol. 100 | no. 9 | 5473-5478


Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration

Peter Teismann*, Kim Tieu*, Dong-Kug Choi*, Du-Chu Wu*, Ali Naini*, Stéphane Hunotdagger , Miquel Vila*, Vernice Jackson-Lewis*, and Serge Przedborski*,Dagger ,§,¶


Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss of the nigrostriatal dopaminergic neurons, which can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Increased expression of cyclooxygenase type 2 (COX-2) and production of prostaglandin E2 have been implicated in neurodegeneration in several pathological settings.

Here we show that COX-2, the rate-limiting enzyme in prostaglandin E2 synthesis, is up-regulated in brain dopaminergic neurons of both PD and MPTP mice.

COX-2 induction occurs through a JNK/c-Jun-dependent mechanism after MPTP administration. We demonstrate that targeting COX-2 does not protect against MPTP-induced dopaminergic neurodegeneration by mitigating inflammation. Instead, we provide evidence that COX-2 inhibition prevents the formation of the oxidant species dopamine-quinone, which has been implicated in the pathogenesis of PD.

This study supports a critical role for COX-2 in both the pathogenesis and selectivity of the PD neurodegenerative process. Because of the safety record of the COX-2 inhibitors, and their ability to penetrate the blood-brain barrier, these drugs may be therapies for PD.

My husband takes Mobic 7.5 mgm/day. one of the neurologists with whom we consulted ~3 yrs ago mentioned that she had quite a number of patients in her practice who reported positive effects from taking Mobic--purely anecdotal; am unsure whether the drug is still under patent, though it has been around for awhile, so my guess is there will not be any studies utilizing this drug for PD--

I don't think Mobic was approved in the US yet when I began etodolac. I'd read about Mobic, and it seems like a great drug. Excellent choice IMHO!

Fish oil also blocks Cox-2.

Mobic is now available generically.

pharmacology:
http://www.uspharmacist.com/oldforma...article_id=617

It is a Cox-1 and Cox-2 inhibitor. It is not specific for only Cox-2.

FYI and an update: my husband stopped Mobic due to increases in one of his renal function blood tests. The results returned to normal after being off this anti inflammatory for 4 weeks.....

... the posted article is technichally beyond me but I take both asprin and Glucosamine as anti-inflamatory... hoping they would help PD (both are relatively safe). any ideas?

Mobic is related to Piroxicam (Feldene) which is the most toxic NSAID, after
Indocin.

I'm sorry your hubby had that happen...but you caught it in time.
It gives me the willies when doctors DON'T supervise this drug properly.
They think it is very "safe" and it is not.

Something of interest which I ran across- Ibuprofen delays or prevents, but most NSAIDs don't. What is different about ibuprofen? In another unrelated abstract I ran across the report that ibuprofen does a similar thing to the NMDA receptors that dextromethorphan cough syrup does. That is an action unrelated to inflammation (or coughing). That doesn't mean that inflammation is not important - in fact, it is critical - but rather that the NMDA receptors are of great importance. They are also the ones that MSG playshell with.

Rick, I've wondered that about ibuprufen with regard to another ailment that I can't think of now.

Similarly Zocor helps to prevent PD but Lipitor does not; both are statins. I think it's because Zocor gets in the brain easier.

Vioxx behaves very differently in the cardiovascular system than celebrex; both are cox-2 inhibitors. It's the law of unintended consequences. Some are good; others are not. Some Cox-2's are good at fighting cancer; others are not.

The makers of the drugs don't seem to spend much time worrying about unintended consequences. Only when they turn out to be good do they pay any attention, with research dollars. It's seems son, anyway.

Here's a bad consequence re: ibuprufen:

I can email the full article if desired.

Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain-derived neurotrophic factor

* Kendra N. Shaw,
* Sean Commins and
* Shane M. O'Mara

Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes prostaglandins from arachidonic acid; it plays a crucial role in inflammation in both central and peripheral tissues.

Here, we describe its role in synaptic plasticity and spatial learning in vivo via an effect on brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa).

We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long-term potentiation (LTP; the major contemporary model of synaptic plasticity), and causes substantial and sustained deficits in spatial learning in the watermaze.

Increases in BDNF and PGE2 following spatial learning and LTP were also blocked. Importantly, 4 days of prior exercise in a running wheel increased endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and restored a parallel increase in LTP and learning-related BDNF and PGE2. In control experiments, we found that BSCI had no effect on baseline synaptic transmission or on the nonhippocampal visible-platform task; there was no evidence of gastric ulceration from BSCI.

COX2 is inhibited by glucorticoids; there was no difference in blood corticosterone levels as measured by radioimmunoassay in any condition.

Thus, COX plays a previously undescribed, permissive role in synaptic plasticity and spatial learning via a BDNF-associated mechanism.

http://www.blackwell-synergy.com/doi...8.2003.02643.x

....The slow, time-dependent, reversible COX inhibitor indomethacin (Dannhardt & Kiefer, 2001) does not, however, block the induction of LTP (Williams & Bliss, 1989; Yamagata et al., 1993); it is possible that the particular pharmacological profile of indomethacin accounts for this lack of an inhibitory effect on LTP. To date, there has been no systematic evaluation of the effects of the many other COX-inhibiting drugs on synaptic plasticity.....

....Apart from these studies, there appear to be few data available on the effects of COX inhibition or activation on synaptic plasticity or learning; the NMDA-receptor-related regulation of COX activity is suggestive of a role for COX in synaptic plasticity (see also Miettinen et al., 1997; who have shown that spreading depression, another form of neuroplasticity, also induces COX-2 activation in cortical neurons)......


....We therefore have provided the first evidence that COX is involved in BDNF expression, LTP and spatial learning; we have provided the first evidence that exercise, which increases levels of endogenous BDNF, also reverses ibuprofen-induced deficit in LTP and spatial learning. We have shown for the first time that PGE2 plays an important regulatory role in synaptic plasticity and learning. We have also confirmed here our previous data (Gooney et al., 2002) showing that both spatial learning and LTP are associated with an increase in BDNF. ....

...Salvemini et al. (1993) found that COX2 is modulated by nitric oxide (NO), a gaseous molecule that plays a role in synaptic plasticity and cellular death. In view of the many regulatory signals involved in COX2 activity and its localization in spines, Kauffman et al. (1996) suggest that COX2 may generate a diffusible signal as a function of the activity at specific synapses. C-fos is rapidly induced by hippocampal NMDA activation and blocked by COX inhibition (Lerea & McNamara, 1993). Because c-fos activity must involve events in the nucleus, it suggests a COX-dependent signal linking receptor activation and gene expression.....