In the reticular activating system (RAS) in the brain stem noradrenaline receptors are excitatory and cause wakefulness, while GABA receptors are inhibitory and cause drowsiness. Caffeine (in coffee, cocoa and cola), theophylline (in tea), amphetamines, ecstasy (MDMA) and cocaine all promote the release of noradrenaline in RAS, so are stimulants. Antidepressant drugs, such as the tricyclics, inhibit the breakdown and absorption of noradrenaline, so extending its effect. Alcohol, benzodiazepines (e.g. mogadon, valium, librium), barbiturates, and marijuana all activate GABA receptors, causing more inhibition of RAS and so are tranquillisers, sedatives and depressants. The narcotics or opioid group of drugs, which include morphine, codeine, opium, methadone and diamorphine (heroin), all block opiate receptors, blocking transmission of pain signals in the brain and spinal chord. The brain’s natural endorphins appear to have a similar action.
The brain neurotransmitter dopamine has a number of roles, including muscle control, pain inhibition and general stimulation. Some psychosis disorders such as schizophrenia and manic depression are caused by an excess of dopamine, and antipsychotic drugs are used to block the dopamine receptors and so reduce its effects. Parkinson’s disease (shaking of head and limbs) is caused by too little dopamine compared to acetylcholine production in the midbrain. The balance can be restored with levodopa, which mimics dopamine, or with anticholinergic drugs (such as procyclidine), which block the muscarinic acetylcholine receptors.
Tetrodotoxin (from the Japanese puffer fish) blocks voltage-gated sodium channels, while tetraethylamonium blocks the voltage-gated potassium channel. Both are powerful nerve poisons. General anaesthetics temporarily inhibit the sodium channels. Strychnine blocks glycine receptors in the brain, causing muscle convulsions and death.
2. Drugs acting on the somatic nervous system
Curare and abungarotoxin (both snake venoms) block the nicotinic acetylcholine receptors in the somatic nervous system, and so relax skeletal muscle. Myasthenia gravis (a weakening of the muscles in the face and throat caused by inactive nicotinic acetylcholine receptors) is treated by the drug neostigmine, which inhibits acetylcholinesterase, so increasing the amount of acetylcholine at the neuromuscular junction.