1,2,3,4-TETRAHYDRO-9-ACRIDINAMINE Property

Melting point:

183.5℃

Boiling point:

325.59°C (rough estimate)

Density 

0.9827 (rough estimate)

refractive index 

1.4400 (estimate)

storage temp. 

4°C, away from moisture and light

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

9?+-.0.20(Predicted)

color 

White to Pale Yellow

CAS DataBase Reference

321-64-2(CAS DataBase Reference)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

1,2,3,4-TETRAHYDRO-9-ACRIDINAMINE Chemical Properties,Usage,Production

Description

In the 1950s, tacrine was used experimentally to reverse cholinergic coma in animals. In the 1960s, tacrine was used to reverse the effects of phencyclidine-like drugs. It was also marketed for many years as a respiratory stimulant. In 1993, the US Food and Drug Administration approved tacrine for the treatment of symptoms of mild to moderate Alzheimer’s disease.

Uses

The current use of tacrine is limited due to its poor oral bioavailability, the necessity for four daily doses, and serious side effects (including nausea, vomiting, dry mouth, indigestion, diarrhea, loss of appetite, urinary incontinence, collapse, convulsions, and hepatotoxicity). Currently, newer cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine) are preferred over tacrine.

Definition

ChEBI: Tacrine is a member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease. It has a role as an EC 3.1.1.7 (acetylcholinesterase) inhibitor. It is a member of acridines and an aromatic amine. It is a conjugate base of a tacrine(1+).

Synthesis Reference(s)

Tetrahedron Letters, 4, p. 1277, 1963 DOI: 10.1039/jr9630005127

Toxicity evaluation

Tacrine has numerous mechanisms of action. The putative principal mechanism of action of tacrine for Alzheimer’s disease is reversible inhibition of acetylcholinesterase (AChE), which thereby slows the breakdown of the chemical messenger acetylcholine (ACh) in the brain. Tacrine also inhibits butyrylcholinesterase activity. In addition, tacrine blocks sodium and potassium channels. Tacrine also acts as a histamine N-methyltransferase inhibitor.
At a therapeutic dose, tacrine causes liver toxicity. Cytotoxicity studies using the human liver cell line HepG2 showed that a therapeutic blood concentration of tacrine induces reactive oxygen species production and glutathione depletion, suggesting that oxidative stress might be involved in tacrine hepatotoxicity.