Dapiprazole
CAS 72822-12-9
HCL SALT 72822-13-0
5,6,7,8-Tetrahydro-3-(2-(4-(O-tolyl)-1-piperazinyl)ethyl)-S-triazolo(4,3-a)pyridine |
Dapiprazole (Rev-Eyes) is an alpha blocker. It is used to reverse mydriasis after eye examination.[1]
Used in the treatment of iatrogenically induced mydriasis produced by adrenergic (phenylephrine) or parasympatholytic (tropicamide) agents used in certain eye examinations.
Dapiprazole is an alpha-adrenergic blocking agent. It produces miosis by blocking the alpha-adrenergic receptors on the dilator muscle of the iris. Dapiprazole produces no significant action on ciliary muscle contraction and thus, there are no changes in the depth of the anterior chamber of the thickness of the lens. It does not alter the IOP either in normal eyes or in eyes with elevated IOP. The rate of pupillary constriction may be slightly slower in clients with brown irises than in clients with blue or green irises.
Dapiprazole acts through blocking the alpha1-adrenergic receptors in smooth muscle. It produces miosis through an effect on the dilator muscle of the iris and does not have any significant activity on ciliary muscle contraction and, therefore does not induce a significant change in the anterior chamber depth or the thickness of the lens.
Oral LD50 is 1189-2100 mg/kg in mice, rats and rabbits.
Brief background information
Salt | ATC | formula | MM | CASE |
---|---|---|---|---|
– | N05AX S01EX02 |
C19H27N5 | 325.46 g / mol | 72822-12-9 |
monogïdroxlorïd | N05AX S01EX02 |
C19H27N5 · HCl | 361.92 g / mol | 72822-13-0 |
Application
-
antipsihoticheskoe means
-
in the treatment of glaucoma
Classes substance
-
Piperazinы
-
1,2,4-triazolo [4,3-a] piridinы
-
Synthesis
Scheme illustration:By cyclization of O-methylvalerolactam (I) with 3-(4-o-tolyl-1-piperazinyl) propionic acid hydrazide (II) in refluxing xylene, followed by a treatment with ethanolic HCl. |
FR 2423221; GB 2020269; JP 54157576; NL 7902489; US 4252721
Acylation of (1-methylcyclopropyl)guanidine (IV) with 3-bromo-5-chlorothiophene-2-sulfonyl chloride (III) under Schotten-Baumann conditions afforded the sulfonyl guanidine (V). This was cyclized to the desired thienothiadiazine upon treatment with Cs2CO3 and Cu2O in boiling butanol.
In a different method, (1-methylcyclopropyl)guanidine (I) is acylated by 3-bromo-5-chlorothiophene-2-sulfonyl chloride (II) to produce the sulfonyl guanidine (III). Intramolecular cyclization of (III) in the presence of Cu2O and Cs2CO3 leads to the title thienothiadiazine derivative. Similarly, acylation of guanidine (I) with 3,5-dichlorothiophene-2-sulfonyl chloride (IV) provides sulfonyl guanidine (V), which is then cyclized in the presence of Cu2O and Cs2CO3.
In an alternative method, sulfonylation of N-isopropylguanidine (V) with 2,5-dichlorothiophene-3-sulfonyl chloride (IV) produced the sulfonyl guanidine (VI). This was then cyclized to the title compound by treatment with copper bronze and potassium carbonate in boiling DMF……..WO 0102410
Trade names
country | Tradename | Manufacturer |
---|---|---|
Germany | Remidrial | winegrower |
Italy | Glamidolo | Angelini, 1987 |
Ukraine | no | no |
Formulations
-
eyedrops 50 mg / 10 ml (5%) (hydrochloride)
References
-
DE 2 915 318 (Angelini; appl. 14.4.1979; I-prior. 18.4.1978).
-
US 4 307 095 (Angelini; 22.12.1981; prior. 29.3.1979, 29.8.1980; I-prior. 18.4.1978).
-
US 4 307 096 (Angelini; 22.12.1981; prior. 29.3.1979, 29.8.1980; I-prior. 18.4.1978).
-
US 4 325 952 (Angelini; 20.4.1982; prior. 29.3.1979, 29.8.1980; I-prior. 18.4.1978).
-
BE 877 161 (Angelini; appl. 21.6.1979).
References
- Doughty, Michael J.; Lyle, William M. (May 1992). “A Review of the Clinical Pharmacokinetics of Pilocarpine, Moxisylyte (Thymoxamine), and Dapiprazole in the Reversal of Diagnostic Pupillary Dilation”. Optometry & Vision Science 69 (5).
- US 4 307 096 (Angelini; 22.12.1981; prior. 29.3.1979, 29.8.1980; I-prior. 18.4.1978).
- US 4 325 952 (Angelini; 20.4.1982; prior. 29.3.1979, 29.8.1980; I-prior. 18.4.1978).
- BE 877 161 (Angelini; appl. 21.6.1979).
- DE 2 915 318 (Angelini; appl. 14.4.1979; I-prior. 18.4.1978).
- US 4 307 095 (Angelini; 22.12.1981; prior. 29.3.1979, 29.8.1980; I-prior. 18.4.1978).
Structural formula
UV- Spectrum
IR – spectrum
Wavelength (μm) |
---|
Wave number (cm -1 ) |
References
-
UV and IR Spectra. H.-W. Dibbern, R.M. Muller, E. Wirbitzki, 2002 ECV
-
NIST/EPA/NIH Mass Spectral Library 2008
-
Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman. Academic Press, 2000.
-
Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.
Systematic (IUPAC) name | |
---|---|
3-{2-[4-(2-methylphenyl)piperazin-1-yl]ethyl}-5,6,7,8-
tetrahydro-[1,2,4]triazolo[4,5-a]pyridine |
|
Clinical data | |
AHFS/Drugs.com | Consumer Drug Information |
MedlinePlus | a601043 |
Pregnancy category |
|
Routes of administration |
Topical (eye drops) |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Bioavailability | Negligible when administered topically |
Identifiers | |
CAS Number | 72822-12-9 |
ATC code | S01EX02 (WHO) |
PubChem | CID 3033538 |
IUPHAR/BPS | 7155 |
DrugBank | DB00298 |
ChemSpider | 2298190 |
UNII | 5RNZ8GJO7K |
KEGG | D07775 |
ChEBI | CHEBI:51066 |
ChEMBL | CHEMBL1201216 |
Chemical data | |
Formula | C19H27N5 |
Molar mass | 325.451 g/mol |
n1nc(n2c1CCCC2)CCN4CCN(c3ccccc3C)CC4
BURMA
HERE ARE MY 10 REASONS WHY YOU SHOULD PACK YOUR BAGS AND HEAD TO BURMA!
01: The People
For true hospitality, travel to Burma
In my travel experience, out of all the
Asians I have met, the Burmese are the kindest, most friendly people who
are willing to go above and beyond to make friends with you, help you
out and make sure you are having a great time in their country. They
always seem to be happy, smiling and keen to practice their English over
a glass of tea! They can be quite a shy people as they are extremely
polite, kids tend to be the exception to the rule – they will always run
up to you to practice their English and unlike the rest of Asia, I was
never once hassled by locals for money. The Burmese left a lasting
impression on me; I felt that I could truly trust them and I made some
incredible connections with locals I met whilst travelling there.
02: Insane Temple Ruins
Get lost in some of the biggest temple ruins in the world
When most people think of lost cities
they immediately think of Angor Wat in Cambodia or maybe Hampi in India
but the ruins of Bagan in central Burma are without a doubt the most
stunning, least touristey, ruins I have ever seen. I spent an incredible
few days exploring by bike, watching the sun set over Bagan’s temple
studded plains and making friends with the local kids out to practice
their English. For the true adventurer, you can head even deeper into
the country’s largely unexplored regions and visit the stunning temple
ruins at Mrauk Au, you will probably have them all to yourself.
03: Real Exploring
Discover the Asia of 100 years ago
Burma is an absolutely massive country
and there are many hidden gems in this astounding country which only the
locals will know about. It is extremely easy to get off the beaten
track and to have temples, ruins, mountains and caves all to yourself.
When backpacking in Burma, I felt like I had stepped back 100 years in
to the past, I felt like a proper explorer. The people who I met in
remote communities in the Shan highlands had often not seen another
westerner for months or even years, this is prime exploring territory.
Whilst exploring the south of the country I came across a huge field of
painted Buddha statues, some were cracked and covered by jungle, others
looked freshly painted. Who built, painted and maintained them? I have
no idea. This is why I love Burma.
04: Trekking
Take to the hills and meet awesome people
Trekking in Burma is a relatively new
activity but already tour agencies are springing up to cater for
adventourous backpackers. Most backpackers opt for a two day trek around
the stilt villages of Inle Lake but for a real experience; head deep
into the Shan highlands or South to Hp-Pan. Here you can summit jungle
clad limestone peaks, many of which are topped by small monastries, and
soak in some spectacular views. Trekking in Burma is a really amazing
experience; I met colourful freshwater crabs, hiked through mist draped
forests and shared tea with novice monks who spoke no English but always
seemed happy to see me.
05: Monks
Spiritual-esque discussions galore
Speaking of Monks, it’s pretty hard to
travel in Burma without meeting a few! I had some amazing discussions
with monks I met in temples, on buses, in the street or even whilst
riding my bicycle. I was told by a monk that 1% of Burma’s entire
population are monks and they certainly seem to be everywhere. Whilst
trekking I met a shy monk working on repairing a temple wall, we chatted
for a while and I spent an hour helping him, he offered me tea and
allowed me to take his photograph. I came away with a much richer
understanding of what Buddhism is all about. The monks are a friendly
bunch and would often ask me all kinds of questions about life outside
Burma, spirituality and even football!
06: Food
“Really? The food’s OK?” I hear you ask…
The food is better than OK, Burmese
cuisine is some of the best in Asia. Sure, there may not be many Burmese
restaurants outside of Burma but that’s largely because the country has
been shut off from the rest of the world for so long. The food is an
eclectic mix of Thai, Chinese and Indian cuisine and basically includes
all the best bits from Thai, Chinese and Indian dishes. Check these
tasty, one of a kind, dishes out:
– Gyin Thohk – tasty ginger salad with sesame seeds.– Fruit Shakes – Keep an eye out for creamy avocado and banana shakes around Inle Lake
– Kat Kyi Hnyat – The Burmese answer to Pad Thai, a gorgeous coastal dish of rice noodles with seafood, meats, raw bean sprouts and fried eggs.
– Danbauk – A tasty Indian inspired curry served with mango pickle, fresh mint and green chili.
– Shan Tofu – Do not miss this awesome home-made tofu from the Shan highlands.
07: Cheap Beer!
Beer for 50 cents?!
I have made it a personal mission to
sample as many local beers throughout the world as I possibly can… so
far, Myanmar Beer is without a doubt my favourite brand. For just 50
cents, you can have a cool, refreshing, tap drawn beer in a iced glass.
For five bucks, you can get well and truly merry. Mandalay Beer makes a
tasty alternative if you get sick of Myanmar Beer but I can guarantee
you won’t.
08: Stunning Islands & Beaches
Burma has a hidden paradise of unexplored beaches and islands
Most Backpackers are not yet aware that
Burma has some of the world’s most beautiful beaches and islands. Until
recently, these palm-fringed, white sand playgrounds were off limits
unless you had a super-yacht handy but this is changing fast and every
week more and more restrictions are being lifted. Now is the perfect
time to travel to Burma and hunt for your dream island; think coral blue
waters, coconut cocktails and perfect sandy beaches, the opportunities
are endless. There are over 800 islands in Burma’s Mergui archipelago
which are currently empty, making this the perfect opportunity to head
out on a kayak or boat and discover paradise in the ocean.
09: Caves
Discover cavernous underground temples filled with Buddha images
When travelling, I’m always looking for adventurous ways to keep myself busy, whether it’s living in a cave with a Bedouin
or mountain biking through the jungles of Laos. In Burma, there is a
ton of activities for the adventurous traveller but one of the best has
got to be exploring some of the huge caves which pockmark the country.
Many of these are not covered by any guidebook, it’s simply a case of
asking around and seeing if there are any cool caves nearby. One of the
biggest which I visited, in the South of the country, was filled with
huge Buddha images and statues as well as some beautiful rock
formations. I walked through it for over an hour, it must have been
about three kilometres long, before I emerged on the other side to find a
hidden lake framed by a backdrop of limestone mountains; to this day it
is still one of the most beautiful things I have discovered whilst
backpacking.
10: It’s changing fast
Now is the time to go!
Burma is well and truly back on the
Backpacker map and in 2014 it has become THE place to go. I was lucky
enough to first visit in 2012 and I met perhaps a dozen backpackers in
my entire time there. These days, more and more backpackers are tagging
Burma on to the classic Thailand – Laos – Vietnam – Cambodia route, and
rightly so! However, as the country continues to open up and as
investment and travelers continue to pour in it is only a matter of time
before some of Burma’s most enchanting attractions become diluted.
Luckily, the country is so big that there is plenty of room and plenty
of wild places left for backpackers to explore. Do not hesitate; visit
this incredible land now, meet the wonderful people, have a beer or
three and explore till your heart’s content.
…AND NOW? PACK YOUR BACKPACK, BOOK YOUR FLIGHT AND GET OUT THERE!!
Need some more information? Check out this travel guide I wrote based on my travels in Burma.