Strychnine - Mechanism

Mechanism

Strychnine is a neurotoxin which acts as an antagonist of glycine and acetylcholine receptors. It primarily affects the motor nerves in the spinal cord which control muscle contraction. An impulse is triggered at one end of a nerve by the binding of neurotransmitters to the receptors. In the presence of neuroinhibitors, a greater quantity of neurotransmitters must bind to receptors before there will be an action potential generated. An example of a neurotransmitter is glycine, which acts primarily as an agonist of the glycine receptor. This is a ligand-gated chloride channel in neurons located in the spinal cord and in the brain. Strychnine is an antagonist of glycine, which means it binds to the same receptor. When strychnine binds to this receptor, glycine is unable to bind to it at the same time. Therefore, the inhibiting effect of glycine is reduced, so nerve impulses are triggered with lower levels of neurotransmitters. When there is no inhibitory effect the motor neurons do not stop their stimulus and the victim will have constant muscle contractions. Structure of strychnine in complex with ACh binding protein (AChBP). Brams et al, PLoS Biol 9:e1001034 2011

Strychnine is also an antagonist for acetylcholine receptors, which is known to be homologous to the glycine receptor.

In low dosages, strychnine can act as a stimulant and has been used by athletes to enhance their performance. Strychnine made headlines back in 1904 during the St. Louis Olympics. At that time there were no rules yet about the use of performance enhancing drugs. The American Fred Lorz won the marathon competition but was disqualified just after crossing the finish line because officials learned he had taken a car ride for part of the race. The next man to finish was the British-born US athlete Thomas Hicks. He won the gold medal but not without a little help. About 10 miles from the finish line Hicks begged his trainers to let him stop running and give-up the race. His trainers refused and gave him a dose of strychnine as a stimulant to keep him going. They also gave him raw egg-white and brandy. As a result Hicks had to be carried across the finish line and it took four doctors to revive him so that he could leave the stadium. More recently at the 1992 Barcelona Olympics, strychnine was used to optimize the athletic performance of Wu Dan, a female volleyball player from China. Dan was the first person to test positive for drugs at the Olympics, testing positive for strychnine despite claiming not having ingested any. The strychnine was contained in capsules that Dan was taking without the knowledge of the team doctor. She took the capsule as a tonic because she was feeling a bit tired. The Olympic committee banned her from any more competition but stated that Dan didn’t intentionally cheat but the mistake was due to poor education.