Question

Given below are two statements, one is labelled as Assertion A and the other is labelled as Reason R:
Assertion A : Tricyclic antidepressants (TCAs) and related drugs inhibit NET and SERT.
Reason R : NET and SERT mediate active reuptake of biogenic amines NA and 5-HT into their respective neurones and thus potentiate TCAs.
In light of the above statements, choose the correct answer from the options given below:

• A. Both A and R are true and R is the correct explanation of A
• B. Both A and R are true but R is NOT the correct explanation of A
• C. A is true but R is false
• D. A is false but R is true

Hint:

To analyze this type of question, look closely at the direction of causality. NET and SERT normally terminate signaling. TCAs inhibit these transporters to potentiate neurotransmitter action, not the other way around.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Neuropharmacology examines how antidepressant drugs modulate synaptic transmission.
Tricyclic antidepressants (TCAs) work by inhibiting the reuptake of key monoamine neurotransmitters, norepinephrine and serotonin, from the synaptic cleft back into presynaptic neurons, thereby prolonging their signaling activity.

Step 2: Detailed Explanation:
Let us analyze both statements:
1. Assertion A: Tricyclic antidepressants (TCAs) and related drugs inhibit NET and SERT.
This statement is correct.
TCAs (such as amitriptyline, clomipramine, and imipramine) block the norepinephrine transporter (NET) and the serotonin transporter (SERT) located on presynaptic neuronal membranes.
This inhibition prevents the reuptake of norepinephrine (NA) and serotonin (5-HT), increasing their concentration and activity within the synaptic cleft.
Therefore, Assertion A is true.
2. Reason R: NET and SERT mediate active reuptake of biogenic amines NA and 5-HT into their respective neurones and thus potentiate TCAs.
This statement is incorrect.
While NET and SERT do mediate the active reuptake of NA and 5-HT to terminate their neurotransmitter signaling, this physiological reuptake process does not "potentiate TCAs."
Instead, it is the inhibition of these transporters by the TCAs that potentiates the action of the neurotransmitters (NA and 5-HT).
The transporters themselves naturally terminate transmitter actions and decrease synaptic signaling, which is opposite to the pharmacological effect of TCAs.
The phrasing "thus potentiate TCAs" is conceptually incorrect because the transporters do not potentiate the drug; rather, the drug inhibits the transporters to potentiate synaptic transmission.
Therefore, Reason R is false.

Step 3: Final Answer:
Assertion A is true, but Reason R is false because the normal function of NET and SERT is to terminate transmitter action, and their inhibition by TCAs is what potentiates synaptic transmission.
Therefore, the correct option is (C).