From the Guidelines
Ativan (Lorazepam) works by enhancing the effects of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain, which helps to calm down excessive neuronal activity [ 1 ].
Mechanism of Action
It is a benzodiazepine medication that activates γ-aminobutyric acid A (GABA) neuronal receptors in the brain, resulting in anxiolytic, amnestic, sedating, hypnotic, and anticonvulsant effects [ 1 ].
Key Points
- The usual dose of Ativan ranges from 1 to 4 milligrams, taken 2 to 3 times a day, with a maximum daily dose of 6 milligrams.
- It is usually taken for a short period, such as 2 to 4 weeks, as long-term use can lead to dependence and withdrawal symptoms.
- Ativan starts to work within 20 to 30 minutes after oral administration, and its effects can last for 6 to 12 hours [ 1 ].
- It is essential to use Ativan under the guidance of a healthcare professional, as they can determine the appropriate dose and duration of treatment based on individual needs and medical history.
Important Considerations
- Elderly patients are significantly more sensitive to the sedative effects of benzodiazepines [ 1 ].
- Benzodiazepines can cause respiratory depression and systemic hypotension, especially when administered in conjunction with other cardiopulmonary depressants, particularly opioids [ 1 ].
From the FDA Drug Label
Studies in healthy volunteers show that in single high doses lorazepam has a tranquilizing action on the central nervous system with no appreciable effect on the respiratory or cardiovascular systems. The mechanism of action of Ativan (Lorazepam) is a tranquilizing action on the central nervous system.
- The exact mechanism is not explicitly described in the label, but it is known to have an effect on the central nervous system (CNS). 2
From the Research
Mechanism of Action of Ativan (Lorazepam)
The mechanism of action of Ativan (Lorazepam) can be understood by examining its effects on the central nervous system, particularly its interaction with gamma-aminobutyric acid (GABA) receptors.
- Lorazepam, like other benzodiazepines, potentiates the neural inhibition mediated by GABA, which is the major inhibitory neurotransmitter in the brain 3, 4.
- The actions of benzodiazepines, including lorazepam, result from their effects on the ionotropic GABA(A) receptors in the central nervous system, where they enhance GABAergic neurotransmission 3, 5.
- Lorazepam does not activate GABA(A) receptors directly but requires the presence of GABA to exert its effects, leading to sedation, hypnosis, decreased anxiety, anterograde amnesia, centrally mediated muscle relaxation, and anti-convulsant activity 3.
- In addition to its central effects, lorazepam has a dose-dependent ventilatory depressant effect and causes a modest reduction in arterial blood pressure and an increase in heart rate due to decreased systemic vascular resistance 3.
- Studies using Positron-Emission Tomography (PET) have shown that lorazepam decreases dopamine D(2)/D(3) receptor binding potential in certain areas of the brain, suggesting that cortical GABA-dopamine interaction may be involved in its central actions 5.
- The sedative effect of lorazepam is associated with a decrease in D(2)/D(3) receptor binding potential in the dorsolateral prefrontal cortex, further supporting the hypothesis of GABA-dopamine interaction in its mechanism of action 5.
- Functional magnetic resonance imaging (fMRI) studies have demonstrated that lorazepam reduces cerebral activity in areas such as the superior frontal gyrus, anterior insula/inferior frontal gyrus, and cingulate gyrus during an anxiety challenge, providing evidence of its modulatory effects on brain activation related to anticipatory anxiety 6.
Key Effects of Lorazepam
- Sedation and hypnosis
- Decreased anxiety
- Anterograde amnesia
- Centrally mediated muscle relaxation
- Anti-convulsant activity
- Dose-dependent ventilatory depressant effect
- Modest reduction in arterial blood pressure and increase in heart rate