The Pharmacological Properties and Therapeutic Use of Apomorphine

Abstract

Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D 1 , D 2S , D 2L , D 3 , D 4 , and D 5 receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT 1A , 5HT 2A , 5HT 2B , and 5HT 2C ), and α-adrenergic receptors (α 1B , α 1D , α 2A , α 2B , and α 2C ). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (i.e., to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer's disease has been suggested; APO seems to stimulate A catabolism in an animal model and cell culture, thus reducing the rate of A oligomerisation and consequent neural cell death.

Role of Apomorphine in the Treatment of Parkinson’s Disease

“…Apomorphine has been long known to act as an erectogenic agent due to its action on dopamine receptors in the CNS. The dopamine receptors in the CNS that are involved in sexual function are mainly the D 2 like receptors in the putamen, thalamus, medial preoptic area nucleus and the paraventricular nucleus, which then project to the spinal cord [6]. Efficacy results were mixed and complicated by typical side effects.…”

“…This results in very high and rapid concentrations of apomorphine in the brain, where it preferentially accumulates. Brain concentrations of apomorphine can be up to eight times higher than those in plasma [6]. The compound is acidic with a pH 3-4, which limits its practical absorption through mucosal tissue [7].…”

“…Elimination is a two-compartment model with the main metabolic route auto-oxidation. Approximately 10 % is transformed in the liver by glucuronidation and sulfation and only approximately 5 % is excreted unchanged in the urine [6,9,15]. Of potential clinical interest, apomorphine is partially metabolized by catecholamine-O-methyl transferase (COMT), which also partially metabolizes LDopa, and can be inhibited with approved medications (entacapone and tolcapone).…”

“…The more severe adverse effects that limited use are development of intravascular thrombosis thought to be due to the crystallization of apomorphine in the catheter. These are rarely used now [6,46].…”

“…AB peptide assembly in the brain forms amyloid plaques, which when accumulated have a neurotoxic effect by promoting a chronic inflammatory state and increased free radial production (H 2 O 2 , O 2 ), apoptosis, and cell death. The potential action of apomorphine on formation of amyloid plaques has generated interest in exploring its therapeutic use for Alzheimer's disease [6,[10][11][12].…”