Tacrine hydrochloride hydrate

Names

[ CAS No. ]:
206658-92-6

[ Name ]:
Tacrine hydrochloride hydrate

[Synonym ]:
1,2,3,4-Tetrahydroacridin-9-amine hydrochloride hydrate
1,2,3,4-Tetrahydro-9-acridinamine hydrochloride hydrate
9-Acridinamine, 1,2,3,4-tetrahydro-, hydrochloride, hydrate (1:1:1)
Tacrine hydrochloride hydrate

Biological Activity

[Description]:

Tacrine hydrochloride hydrate is an inhibitor of both acetyl (AChE) and butyryl-cholinestrase (BChE) with IC50s of 31 nM and 25.6 nM, respectively.

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> AChE

Research Areas >> Neurological Disease

[Target]

IC50: 31 nM (AChE), 25.6 nM (BChE)

[In Vitro]

Tacrine hydrochloride hydrate (12.5 to 37.5 nM) inhibits venom acetylcholinesterase as well as human serum butyrylcholinesterase in a concentration-dependent manner. The IC50 is 31 nM for snake venom AChE and 25.6 nM for human BChE[1].

[In Vivo]

Pretreatment with Tacrine hydrochloride hydrate also modifies absolute levels of cocaine self-administration during reacquisition. Body weight declines approximately one-half percent over four days of treatment with intravenous Tacrine hydrochloride hydrate. Delivery of Tacrine hydrochloride hydrate by osmotic pump does not alter either linear- or repeated- cocaine-induced locomotor activity. There is no significant main effect or interaction with Tacrine hydrochloride hydrate treatment on active lever responding during reinstatement. Post hoc comparisons indicate that rats self-administering cocaine has significantly lower alkaline phosphatase levels, relative to Tacrine hydrochloride hydrate- but not saline- treated rats evaluated by conditioned-place preference[2].

[Kinase Assay]

The kinetic parameters of the interaction between Tacrine hydrochloride hydrate and cholinesterase are determined using the double reciprocal plot analyzed over a range of acetylthiocholine concentrations (0.05 to 1 mM) in the absence and in the presence of Tacrine hydrochloride hydrate (12.5 to 37.5 nM). IC50 is determined by percentage residual activity versus concentration of Tacrine hydrochloride hydrate[1].

[Animal admin]

Male Wistar rats at 9 weeks of age are used in this study. As soon as rats exhibit a stable pattern of self-administration under fixed-ratio-5 (FR-5) with a 20-second time out, sessions are discontinued over 24 hours and rats are left undisturbed in home cages, attached to a fluid swivel and steel-coil tether. This initial washout interval is assessed as more than adequate to allow clearance of plasma cocaine, which has a half-life of less than 20 minutes in rats. Beginning on the following day, 10 mg/kg-day of Tacrine hydrochloride hydrate or vehicle (saline) is administered as a chronic infusion over 4 days, delivered intravenously at 4.0 ml per day. After completion of these infusions, rats are then left undisturbed in home cages for an additional two days. This second washout period permits complete clearance of Tacrine hydrochloride hydrate, which has a half-life of less than two hours in rat brain. Cocaine self-administration is then re-initiated under FR-5 with a 20-second time-out period. To determine persistent effects of Tacrine hydrochloride hydrate, the pattern of self-administration is monitored over six additional sessions[2].

[References]

[1]. Ahmed M, et al. Inhibition of two different cholinesterases by tacrine. Chem Biol Interact. 2006 Aug 25;162(2):165-71.

[2]. Grasing K, et al. Enduring effects of tacrine on cocaine-reinforced behavior: Analysis by conditioned-place preference, temporal separation from drug reward, and reinstatement. Pharmacol Res. 2015 Jul;97:40-7.

[Related Small Molecules]

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₃H₁₇ClN₂O

[ Molecular Weight ]:
252.740

[ Exact Mass ]:
252.102936

[ Storage condition ]:
-20℃

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H311-H315-H319-H331-H335-H351

[ Precautionary Statements ]:
P261-P280-P301 + P310-P305 + P351 + P338-P311

[ RIDADR ]:
UN 2811 6.1 / PGIII

Articles

Synthesis, biological activity, and biopharmaceutical characterization of tacrine dimers as acetylcholinesterase inhibitors.

Int. J. Pharm. 477(1-2) , 442-53, (2014)

Tacrine (THA), as the first approved acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD), has been extensively investigated in last seven decades. After dimerization o...

Influence of electronic and formulation variables on transdermal iontophoresis of tacrine hydrochloride.

Pharm. Dev. Technol. 20 , 442-57, (2015)

Freshly excised rat skin and side-by-side permeation cells were used to study the effect of electronic and formulation variables on transdermal iontophoretic delivery of tacrine. Current strength at 0...

Tacrine sinusoidal uptake and biliary excretion in sandwich-cultured primary rat hepatocytes.

J. Pharm. Pharm. Sci. 17(3) , 427-38, (2014)

PURPOSE. The knowledge of hepatic disposition kinetics of tacrine, a first cholinesterase inhibitor was approved by FDA for the treatment of Alzheimer's disease (AD), would help to understand its hepa...