Intranasal anticonvulsive treatment: A prospective management of intractable epilepsy

[Dutch mom]

... Recently, intrinsic or acquired overexpression of multidrug transporters in the blood-brain barrier has been suggested to result in producing pharmacoresistance in epilepsy, for anti-epileptic drugs concentrations would be reduced to the level that is insufficient to cause anti-epileptic activity. Intranasal administration provides a direct transport pathway to brain tissue that circumvents the blood-brain barrier for many drugs and neuropeptides. These significant conditions support the hypothesis that intranasal anticonvulsive treatment may be a prospective management of intractable epilepsy. ...

http://highwire.stanford.edu/cgi/medline/pmid;18614291

The blood brain barrier (BBB) represents one of the strictest barriers of in vivo therapeutic drug delivery. The barrier is defined by restricted exchange of hydrophilic compounds, small proteins and charged molecules between the plasma and central nervous system (CNS). For decades, the BBB has prevented the use of many therapeutic agents for treating Alzheimer's disease, stroke, brain tumor, head injury, spinal cord injury, depression, anxiety and other CNS disorders. Different attempts were made to deliver the drug across the BBB such as modification of therapeutic agents, altering the barrier integrity, carrier-mediated transport, invasive techniques, etc. However, opening the barrier by such means allows entry of toxins and undesirable molecules to the CNS, resulting in potentially significant damage. An attempt to overcome the barrier in vivo has focused on bypassing the BBB by using a novel, practical, simple and non-invasive approach i.e. intranasal delivery. This method works because of the unique connection which the olfactory and trigeminal nerves (involved in sensing odors and chemicals) provide between the brain and external environments. The olfactory epithelium acting as a gateway for substances entering the CNS and peripheral circulation is well known. Also, it is common knowledge that viral infections such as common cold, smallpox, measles, and chicken pox take place through the nasopharynx. The neural connections between the nasal mucosa and the brain provide a unique pathway for the non-invasive delivery of therapeutic agents to the CNS. This pathway also allows drugs which do not cross the BBB to enter the CNS and it eliminates the need for systemic delivery and thereby reducing unwanted systemic side effects. Intranasal delivery does not require any modification of therapeutic agents and does not require that drugs be coupled with any carrier. A wide variety of therapeutic agents, including both small molecules and macromolecules can be rapidly delivered to the CNS using this method. The present review discusses the various applications, advantages and limitations of this novel approach. ...

http://www.ijp-online.com/text.asp?2004/36/3/140/6866

I know intranasal midazolam being effective as an emergency med to some children with intractalbe seizures while midazolam tablets and liquid fail to stop their seizures.

Maybe intranasal admission of anti-epileptic drug could be a future solution?

[Bernard]

Nice find. I notice that the articles are several years old already. I wonder why more anti-epileptic drugs aren't available for intranasal delivery yet.