 In addition to their reuptake inhibition, many TCAs also have high affinity as antagonists at the 5-HT2 (5-HT2A and 5-HT2C), 5-HT6, 5-HT7, α1-adrenergic, and NMDA receptors, and as agonists at the sigma receptors (σ1 and σ2), some of which may contribute to their therapeutic efficacy, as well as their side effects.The TCAs also have varying but typically high affinity for antagonising the H1 and H2 histamine receptors, as well as the muscarinic acetylcholine receptors.As a result, they also act as potent antihistamines and anticholinergics.