Ciclazindol

Ciclazindol
Clinical data
Routes of
administration		Oral
ATC code
  • none
Pharmacokinetic data
MetabolismRenal[1]
Elimination half-life~32 hours[1]
ExcretionUrine, feces[1]
Identifiers
  • 10-(3-chlorophenyl)-3,4-dihydro-2H-pyrimido[1,2-a]indol-10-ol
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H15ClN2O
Molar mass298.77 g·mol−1
3D model (JSmol)
  • Clc1cccc(c1)C3(O)c4c(N2\C3=N/CCC2)cccc4

Ciclazindol (WY-23409) is an antidepressant and anorectic[2] drug of the tetracyclic[citation needed] chemical class that was developed in the mid to late 1970s, but was never marketed.[3][4] It acts as a norepinephrine reuptake inhibitor, and to a lesser extent as a dopamine reuptake inhibitor.[3][5] 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.[5][6][7] As suggested by its local anesthetic properties,[6] ciclazindol may also inhibit sodium channels. It is known to block potassium channels as well.[8][9]

The dosage in human volunteers is stated to be 25mg daily.[1] However, doses of up to 200mg have also been reported.[2] 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).[10]

  1. ^ a b c d Swaisland AJ, Franklin RA, Southgate PJ, Coleman AJ (February 1977). "The pharmacokinetics of ciclazindol (Wy 23409) in human volunteers". British Journal of Clinical Pharmacology. 4 (1): 61–65. doi:10.1111/j.1365-2125.1977.tb00668.x. PMC 1428987. PMID 843425.
  2. ^ a b Lean ME, Borthwick LJ (1983). "Ciclazindol: an oral agent with weight reducing properties and hypoglycaemic activity". European Journal of Clinical Pharmacology. 25 (1): 41–5. doi:10.1007/BF00544012. PMID 6352281. S2CID 30435450.
  3. ^ a b Ghose K, Rama Rao VA, Bailey J, Coppen A (April 1978). "Antidepressant activity and pharmacological interactions of ciclazindol". Psychopharmacology. 57 (1): 109–114. doi:10.1007/BF00426966. PMID 96461. S2CID 12961802.
  4. ^ Levine S (1979). "A controlled comparative trial of a new antidepressant, ciclazindol". The Journal of International Medical Research. 7 (1): 1–6. doi:10.1177/030006057900700101. PMID 369921. S2CID 28112402.
  5. ^ a b Oh VM, Ehsanullah RS, Leighton M, Kirby MJ (January 1979). "Influence of ciclazindol on monoamine uptake and CNS function in normal subjects". Psychopharmacology. 60 (2): 177–181. doi:10.1007/BF00432290. PMID 106428. S2CID 24199961.
  6. ^ a b Waterfall JF, Smith MA, Gaston WH, Maher J, Warburton G (July 1979). "Cardiovascular and autonomic actions of ciclazindol and tricyclic antidepressants". Archives Internationales de Pharmacodynamie et de Therapie. 240 (1): 116–136. PMID 507990.
  7. ^ Gardner CR, Wilford AE (January 1980). "The effects of mianserine, amitriptyline, ciclazindol and viloxazine on presynaptic alpha-receptors in isolated rat atria [proceedings]". British Journal of Pharmacology. 68 (1): 184P–185P. doi:10.1111/j.1476-5381.1980.tb10705.x. PMC 2044122. PMID 6244029.
  8. ^ Noack T, Edwards G, Deitmer P, Greengrass P, Morita T, Andersson PO, et al. (May 1992). "The involvement of potassium channels in the action of ciclazindol in rat portal vein". British Journal of Pharmacology. 106 (1): 17–24. doi:10.1111/j.1476-5381.1992.tb14286.x. PMC 1907450. PMID 1504725.
  9. ^ Lee K, Khan RN, Rowe IC, Ozanne SE, Hall AC, Papadakis E, et al. (April 1996). "Ciclazindol inhibits ATP-sensitive K+ channels and stimulates insulin secretion in CR1-G1 insulin-secreting cells". Molecular Pharmacology. 49 (4): 715–720. PMID 8609901.
  10. ^ Houlihan WJ, Boja JW, Parrino VA, Kopajtic TA, Kuhar MJ (December 1996). "Halogenated mazindol analogs as potential inhibitors of the cocaine binding site at the dopamine transporter". Journal of Medicinal Chemistry. 39 (25): 4935–4941. doi:10.1021/jm960288w. PMID 8960553.