Toxicology 147 (2000) 33 – 39 Kinetic analysis of the toxicological effect of tacrine (Cognex ® ) on human retinal acetylcholinesterase activity Abdullah S. Alhomida a , Ali A. Al-Rajhi b , Mohammad A. Kamal a , Abdulaziz A. Al-Jafari a, * a Department of Biochemistry, College of Science, King Saud Uniersity, PO Box 2455, Riyadh 11451, Saudi Arabia b King Khalid Eye Specialist Hospital, Riyadh, Saudi Arabia Received 29 April 1999; accepted 18 February 2000 Abstract For the first time, kinetic parameters of the effect of tacrine, an anti-cholinesterase inhibitor of therapeutic potential in Alzheimer’s disease has been studied on human retinal acetyl-cholinesterase (AChE). Tacrine inhibited the AChE activity in a concentration dependent manner, the IC 50 being about 45 nM. The Michaelis–Menten constant (K m ) for the hydrolysis of acetylthiocholine iodide was found to be 0.120 mM and this value was increased by 4–52.8% in the presence of tacrine. V max was observed to be 2.23 mol/h per mg protein for the control system, while it was decreased by 14.73–56.25% in the tacrine treated systems. Dixon as well as Lineweaver–Burk plots and their secondary replots indicated that the nature of the inhibition was of the mixed type, i.e. a combination of competitive and noncompetitive inhibition. The values of K i and K I were estimated to be as 37.76 and 64.36 nM, respectively. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Acetylcholinesterase; Alzheimer’s disease; Inhibition; Kinetics; Tacrine; Retina www.elsevier.com/locate/toxicol 1. Introduction Treatments for the Alzheimer’s disease (AD) facilitating cholinergic function in the central ner- vous system still receives by far the greatest atten- tion, due to its involvement in learning and memory processing (Deutsch, 1985). Pharmaco- logic strategies for AD treatment have focused on increasing cholinergic neuro transmission via di- rect stimulation of muscarinic (Avery et al., 1997), and nicotinic receptors (Newhouse et al., 1997), and via inhibition of acetylcholinesterase, (AChE; EC 3.1.1.7) (Kasa et al., 1997). The classical role of this enzyme is termination of impulse trans- mission at cholinergic synapses by rapid hydroly- sis of the neurotransmitter acetylcholine (ACh) Abbreiations: AChE, acetylcholinesterase; ASCh, acetylth- iocholine iodide; K m , Michaelis – Menten constant. * Corresponding author. Fax: +966-1-4675791. E-mail address: jafari@ksu.edu.sa (A.A. Al-Jafari) 0300-483X/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII:S0300-483X(00)00177-3