Ciclazindol

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = 10-(3-chlorophenyl)-3,4-dihydro-2H-pyrimido[1,2-a]indol-10-ol

| image = Ciclazindol structure.svg

| image_class = skin-invert-image

| tradename =

| pregnancy_category =

| legal_status =

| routes_of_administration = Oral

| bioavailability =

| protein_bound =

| metabolism = Renal{{cite journal | vauthors = Swaisland AJ, Franklin RA, Southgate PJ, Coleman AJ | title = The pharmacokinetics of ciclazindol (Wy 23409) in human volunteers | journal = British Journal of Clinical Pharmacology | volume = 4 | issue = 1 | pages = 61–65 | date = February 1977 | pmid = 843425 | pmc = 1428987 | doi = 10.1111/j.1365-2125.1977.tb00668.x }}

| elimination_half-life = ~32 hours

| excretion = Urine, feces

| CAS_number = 37751-39-6

| ATC_prefix = none

| ATC_suffix =

| PubChem = 37825

| ChemSpiderID = 34683

| ChEMBL = 1192491

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = Y3I9520J7P

| KEGG = D03486

| C=17 | H=15 | Cl=1 | N=2 | O=1

| smiles = Clc1cccc(c1)C3(O)c4c(N2\C3=N/CCC2)cccc4

}}

Ciclazindol (WY-23409) is an antidepressant and anorectic{{cite journal | vauthors = Lean ME, Borthwick LJ | title = Ciclazindol: an oral agent with weight reducing properties and hypoglycaemic activity | journal = European Journal of Clinical Pharmacology | volume = 25 | issue = 1 | pages = 41–5 | date = 1983 | pmid = 6352281 | doi = 10.1007/BF00544012 | s2cid = 30435450 }} drug of the tetracyclic{{cn|date=January 2023}} chemical class that was developed in the mid to late 1970s, but was never marketed.{{cite journal | vauthors = Ghose K, Rama Rao VA, Bailey J, Coppen A | title = Antidepressant activity and pharmacological interactions of ciclazindol | journal = Psychopharmacology | volume = 57 | issue = 1 | pages = 109–114 | date = April 1978 | pmid = 96461 | doi = 10.1007/BF00426966 | s2cid = 12961802 }}{{cite journal | vauthors = Levine S | title = A controlled comparative trial of a new antidepressant, ciclazindol | journal = The Journal of International Medical Research | volume = 7 | issue = 1 | pages = 1–6 | year = 1979 | pmid = 369921 | doi = 10.1177/030006057900700101 | s2cid = 28112402 }} It acts as a norepinephrine reuptake inhibitor, and to a lesser extent as a dopamine reuptake inhibitor.{{cite journal | vauthors = Oh VM, Ehsanullah RS, Leighton M, Kirby MJ | title = Influence of ciclazindol on monoamine uptake and CNS function in normal subjects | journal = Psychopharmacology | volume = 60 | issue = 2 | pages = 177–181 | date = January 1979 | pmid = 106428 | doi = 10.1007/BF00432290 | s2cid = 24199961 }} Ciclazindol has no effects on the SERT, 5-HT receptors, mACh receptors, or α-adrenergic receptors, and has only weak affinity for the H₁ receptor.{{cite journal | vauthors = Waterfall JF, Smith MA, Gaston WH, Maher J, Warburton G | title = Cardiovascular and autonomic actions of ciclazindol and tricyclic antidepressants | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 240 | issue = 1 | pages = 116–136 | date = July 1979 | pmid = 507990 }}{{cite journal | vauthors = Gardner CR, Wilford AE | title = The effects of mianserine, amitriptyline, ciclazindol and viloxazine on presynaptic alpha-receptors in isolated rat atria [proceedings] | journal = British Journal of Pharmacology | volume = 68 | issue = 1 | pages = 184P–185P | date = January 1980 | pmid = 6244029 | pmc = 2044122 | doi = 10.1111/j.1476-5381.1980.tb10705.x }} As suggested by its local anesthetic properties, ciclazindol may also inhibit sodium channels. It is known to block potassium channels as well.{{cite journal | vauthors = Noack T, Edwards G, Deitmer P, Greengrass P, Morita T, Andersson PO, Criddle D, Wyllie MG, Weston AH | display-authors = 6 | title = The involvement of potassium channels in the action of ciclazindol in rat portal vein | journal = British Journal of Pharmacology | volume = 106 | issue = 1 | pages = 17–24 | date = May 1992 | pmid = 1504725 | pmc = 1907450 | doi = 10.1111/j.1476-5381.1992.tb14286.x }}{{cite journal | vauthors = Lee K, Khan RN, Rowe IC, Ozanne SE, Hall AC, Papadakis E, Hales CN, Ashford ML | display-authors = 6 | title = Ciclazindol inhibits ATP-sensitive K+ channels and stimulates insulin secretion in CR1-G1 insulin-secreting cells | journal = Molecular Pharmacology | volume = 49 | issue = 4 | pages = 715–720 | date = April 1996 | pmid = 8609901 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8609901 }}

The dosage in human volunteers is stated to be 25mg daily. However, doses of up to 200mg have also been reported. This is surprising since the dosage of mazindol is only 2-4mg per day.

Ciclazindol is reported to have an IC50 of 1.3nM for the dopamine transporter (cmp 23).{{cite journal | vauthors = Houlihan WJ, Boja JW, Parrino VA, Kopajtic TA, Kuhar MJ | title = Halogenated mazindol analogs as potential inhibitors of the cocaine binding site at the dopamine transporter | journal = Journal of Medicinal Chemistry | volume = 39 | issue = 25 | pages = 4935–4941 | date = December 1996 | pmid = 8960553 | doi = 10.1021/jm960288w }}