5-Hydroxytryptamine1A agonists: potential use in glaucoma. Evidence from animal studies.
Various classes of compounds exist to lower intraocular pressure (IOP) in the treatment of glaucoma. None of them is ideal since some patients respond better than others and the side effects vary between individuals. New classes of compounds need to be introduced to allow the clinician greater scope for effective treatment of all patients. It is now generally agreed that the cause of ganglion cell dysfunction in glaucoma is likely to be multifactorial and that concentrating solely on reducing IOP is inadequate. Irrespective of the reason for the dysfunction, the future goal must be to attenuate cell death. This may be achieved with drugs that interact with components of the retina, and is termed 'neuroprotection'. Thus, drugs that can both reduce IOP and act as neuroprotectants would be ideal for the treatment of glaucoma. In this article we summarise studies on animals which show serotonergic 5-HT1A agonists to both reduce IOP when topically applied to the rabbit eye and blunt the damaging effect to the rat retina and ganglion cells induced by glutamate toxicity or ischaemia. Reduction of IOP occurs via stimulation of 5-HT1A receptors associated with the ciliary processes. Neuroprotection of retinal neurones appears to involve the interaction of 5-HT1A agonists with membrane sodium channels and/or 5-HT1A or even possibly 5-HT7 receptors. Various 5-HT1A agonists are used in patients to treat depression, so classes of these drugs have a proven safety profile for use in patients. The animal studies summarised in this article suggest that 5-HT1A agonists need to be considered as a new class of drugs for the treatment of glaucoma.
Osborne
N N
NN
Nuffield Laboratory of Ophthalmology, University of Oxford, UK. neville.osborne@eye.ox.ac.uk
Wood
J P
JP
Melena
J
J
Chao
H M
HM
Nash
M S
MS
Bron
A J
AJ
Chidlow
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000819:agonists / Q000627:therapeutic use; D000818:Animals; D005901:Glaucoma / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin