D1like

D1like refers to the D1-like family of dopamine receptors, which includes the D1 and D5 subtypes. These G protein–coupled receptors primarily couple to Gs/olf proteins to stimulate adenylyl cyclase, increasing intracellular cyclic AMP (cAMP) and activating protein kinase A. This signaling cascade modulates neuronal excitability and synaptic plasticity, often through phosphorylation of targets such as DARPP-32.

Distribution and pharmacology: D1 and D5 receptors are widely expressed in the brain, with high levels in the striatum and cortex and substantial presence in limbic regions. D1 and D5 receptors share overlapping ligand sensitivity, but some ligands show preferential affinity. Endogenous dopamine activates D1-like receptors, while pharmacological agents include selective agonists and antagonists used in research and, to a limited extent, clinical exploration. Common examples include D1-selective antagonists and nonselective D1/D5 agonists used in preclinical studies.

Functional roles: D1-like signaling contributes to the regulation of motor control, cognition, reward, and reinforcement learning. In basal ganglia circuits, D1 receptor activation in the direct pathway tends to promote movement, while D5 receptors are implicated in learning and emotional processing. D1-like receptors modulate glutamatergic transmission and interact with other neurotransmitter systems, including dopaminergic D2-like receptors, to shape complex behaviors.

Clinical relevance: Altered D1-like signaling has been implicated in movement disorders, schizophrenia, and substance use disorders. Therapeutic strategies have explored targeting D1-like receptors, though achieving selective modulation with favorable safety and efficacy remains challenging. D1 and D5 receptors are the subject of ongoing basic and translational research, particularly regarding cognitive enhancement and neuropsychiatric conditions.

See also: Dopamine receptor, D2-like receptors, G protein–coupled receptors.