Potential treatment for SPMS and/or PPMS
Posted: Fri Mar 15, 2013 11:40 am
Combination of Dizocilpine (NMDA receptor blocker) and Nimodipine (ca-channel blocker, maybe nifedipine too?) may help SPMS and PPMS via neuroprotection, reduced spasticity, and potentially increased cerebral perfusion if vasospasms are a factor.
dizocilpine http://en.wikipedia.org/wiki/Dizocilpine
nimodipine http://en.wikipedia.org/wiki/Nimodipine (do NOT mix with zanaflex http://www.thisisms.com/forum/regimens- ... html#p8952)
Neuroprotection:
Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis 2008 Full Text
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267014/
http://www.thisisms.com/forum/general-d ... tml#p91543
Spasticity:
Ca-channel blockers reduce neuronal excitability.
http://www.medmerits.com/index.php/arti ... sticity/P5
Everything seems related to vasospasm. Since we don't know this is a factor, not bogging thread down with studies.
Random benefits:
Nimodipine and nifedipine enhance transmission at the Schaffer collateral CA1 pyramidal neuron synapse (might help w/adrenal issues)
http://link.springer.com/article/10.100 ... 78?LI=true
Relief from post-O(rgasm) headaches
http://onlinelibrary.wiley.com/doi/10.1 ... ated=false
dizocilpine http://en.wikipedia.org/wiki/Dizocilpine
nimodipine http://en.wikipedia.org/wiki/Nimodipine (do NOT mix with zanaflex http://www.thisisms.com/forum/regimens- ... html#p8952)
Neuroprotection:
Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis 2008 Full Text
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267014/
http://www.ncbi.nlm.nih.gov/pubmed/8819136Our data demonstrate the neuroprotective effect of treatment with a fullerene compound combined with a NMDA receptor antagonist, which may be useful in the treatment of progressive MS and other neurodegenerative diseases.
A JackD post about calcium channel blockersIn vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine: combined therapy and temporal course of protection.
Stuiver BT, Douma BR, Bakker R, Nyakas C, Luiten PG.
Source
Department of Animal Physiology, University of Groningen, Haren, The Netherlands.
Abstract
Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective potential of this combined drug treatment before and after NMDA-exposure. NMDA was unilaterally injected in the magnocellular nucleus basalis (MBN). Neuronal damage was assessed 12 days after the NMDA-injection by measuring the reduction of cholinergic cortical fibres that originate from the MBN neurons. In controls that received no drug treatment, NMDA-exposure damaged MBN neurons such that 66% of the cholinergic terminals were lost in the ipsilateral parietal cortex. Pretreatment with a nimodipine diet (860 ppm) combined with application of MK-801 (5 mg/kg i.p.) before NMDA-exposure reduced fibre loss by 89% thereby providing a near complete neuroprotection. Combined therapy of MK-801 (5 mg/kg i.p.) and nimodipine (15 mg/kg i.p.) 8 min after NMDA-infusion reduced neuronal injury by 82%, while the same combination given 2 h after the excitotoxic treatment still yielded a 66% protection against neurotoxic damage invoked by NMDA. In conclusion, the present data show that a dual blockade of NMDA-channels and voltage-dependent calcium channels (VDCC's) up to 2 h after NMDA-exposure is able to provide a significant protection against NMDA-neurotoxicity.
http://www.thisisms.com/forum/general-d ... tml#p91543
Spasticity:
Ca-channel blockers reduce neuronal excitability.
http://www.medmerits.com/index.php/arti ... sticity/P5
Increased cerebral perfusion:The neuropathophysiologic processes involved in spasticity are complex and not fully understood, but there is a widely accepted hypothesis that spasticity depends on hyperexcitability of spinal alpha motor neurons, which is due to the interruption of descending modulatory influences carried by the corticospinal, vestibulospinal, and reticulospinal tracts and other possible tracts (Filloux 1996). Ia afferent fibers provide segmental input from muscle spindles to alpha motor neuron pools. They synapse on segmental inhibitory interneurons that then inhibit alpha motor neurons innervating antagonist muscles in the Ia reciprocal inhibition pathway. Ib afferents inhibit alpha motor neurons by way of the Golgi tendon organs via the Ib inhibitory interneuron in another pathway known as nonreciprocal inhibition (Young 1994; Filloux 1996). Increased excitation of these afferents does not seem to be the cause of spasticity. Instead, evidence supports that reduced reciprocal inhibition of antagonist motor neuron pools by Ia afferents, decreased presynaptic inhibition of Ia afferents, and decreased nonreciprocal inhibition by Ib terminals are all possible pathophysiologic mechanisms of spasticity (Young 1994). The pathophysiology of traumatic brain injury involves a complex combination of forces that has been a subject of substantial debate (Drew and Drew 2004). On occasion, autonomic dysreflexia may occur after an intramuscular injection, although this is relatively rare (Selcuk et al 2004). In some patients, autonomic dysreflexia may occur even if the level of spinal injury is below T6 (Blackmer 2003; Krassioukov et al 2003). The use of antihypertensive pharmacologic agents in treating spasticity is unclear because randomized trials have not been performed. Nifedipine has been used in a bit-and-swallow technique; more recently, captopril also has been found to be of benefit (Esmail et al 2002).
Everything seems related to vasospasm. Since we don't know this is a factor, not bogging thread down with studies.
Random benefits:
Nimodipine and nifedipine enhance transmission at the Schaffer collateral CA1 pyramidal neuron synapse (might help w/adrenal issues)
http://link.springer.com/article/10.100 ... 78?LI=true
Relief from post-O(rgasm) headaches
http://onlinelibrary.wiley.com/doi/10.1 ... ated=false