PATHOPHYSIOLOGY
1. GLYCINE
The binding of glycine to its receptor on postsynaptic neurons is blocked by the poison
strychnine thus blocking glycine’s inhibitory actions.
The block of inhibition leads to hyper-excitation and typically a patient with strychinine
poisoning asphyxiates due to an inability to relax the diaphragm.
2. GABA
One explanation for the establishment of focal epilepsy is decreased local GABA-
mediated inhibition.
Many facets of epilepsy can be elicited experimentally by blocking GABA inhibition
receptors with the toxin Picrotoxin.
The decrease in GABA inhibition permits cells to fire synchronously, thus producing
massive local excitation and initiation of a seizure.
Clinically, seizures can often be terminated by inducing a barbiturate coma. High dose
barbiturates presumably potentiate GABA’s inhibitory effects preventing local hyper-
excitation by hyperpolarizing the cell membranes.
Mood disorders (generalized anxiety disorder) can also be controlled by drugs which
potentiate GABA’s inhibitory activity.
Some of the most widely prescribed drugs benzodiazepines (Librium and Valium) –
produce their pharmacological effects by increasing GABA’s ability to hyperpolarize
neuronal membranes, thereby quieting the system.
3. NITRIC OXIDE (NO)
NO in excess is toxic to cells.
However, a paradox exits for NO toxicity.
Cells that produce high levels of NO are resistant to its toxic effects.
1
, NO toxicity is used by macrophages and neutrophils as a mechanism to kill tumor cells
and bacteria.
Excess production of NO is thought to play some role in the neuronal loss due to its
toxicity when produced in excess.
4. ACETYLCHOLINE (ACh)
a. Alzheimer’s disease
A disease in which a marked deterioration occurs in the CNS.
The hallmark of this condition is a progressive dementia.
The main characteristic of this disease is a marked decrease in ACh concentrations in the
cerebral cortex and Caudate Nucleus.
b. Myasthenia gravis
A disease of the neuromuscular junction.
The receptors for ACh are destroyed through the actions of the patient’s own antibodies.
2
1. GLYCINE
The binding of glycine to its receptor on postsynaptic neurons is blocked by the poison
strychnine thus blocking glycine’s inhibitory actions.
The block of inhibition leads to hyper-excitation and typically a patient with strychinine
poisoning asphyxiates due to an inability to relax the diaphragm.
2. GABA
One explanation for the establishment of focal epilepsy is decreased local GABA-
mediated inhibition.
Many facets of epilepsy can be elicited experimentally by blocking GABA inhibition
receptors with the toxin Picrotoxin.
The decrease in GABA inhibition permits cells to fire synchronously, thus producing
massive local excitation and initiation of a seizure.
Clinically, seizures can often be terminated by inducing a barbiturate coma. High dose
barbiturates presumably potentiate GABA’s inhibitory effects preventing local hyper-
excitation by hyperpolarizing the cell membranes.
Mood disorders (generalized anxiety disorder) can also be controlled by drugs which
potentiate GABA’s inhibitory activity.
Some of the most widely prescribed drugs benzodiazepines (Librium and Valium) –
produce their pharmacological effects by increasing GABA’s ability to hyperpolarize
neuronal membranes, thereby quieting the system.
3. NITRIC OXIDE (NO)
NO in excess is toxic to cells.
However, a paradox exits for NO toxicity.
Cells that produce high levels of NO are resistant to its toxic effects.
1
, NO toxicity is used by macrophages and neutrophils as a mechanism to kill tumor cells
and bacteria.
Excess production of NO is thought to play some role in the neuronal loss due to its
toxicity when produced in excess.
4. ACETYLCHOLINE (ACh)
a. Alzheimer’s disease
A disease in which a marked deterioration occurs in the CNS.
The hallmark of this condition is a progressive dementia.
The main characteristic of this disease is a marked decrease in ACh concentrations in the
cerebral cortex and Caudate Nucleus.
b. Myasthenia gravis
A disease of the neuromuscular junction.
The receptors for ACh are destroyed through the actions of the patient’s own antibodies.
2
