Drugs interacting with G protein alpha subunits: selectivity and perspectives

Fundam Clin Pharmacol. 1998;12(2):121-32. doi: 10.1111/j.1472-8206.1998.tb00932.x.


Extracellular signal molecules as diverse as hormones, neurotransmitters and photons use a signal transduction pathway involving a receptor, a G protein and effectors. Compounds that interact directly with G proteins can mimic the receptor-G protein interaction or can block the activation of G proteins by receptors. Several binding sites exist on the G alpha protein that may be exploited for the design of synthetic stimulatory or inhibitory ligands. The effector binding site is regulated by endogenous proteins and appears to be a target for selective exogenous ligands. The GTP binding site presents a large homology within the G protein families and therefore the nucleotide analogs might not be considered as a tool to discriminate between the G protein subclasses. In contrast, different experimental strategies have substantiated the specificity in the interaction between a receptor and a G protein, the receptor binding site of G proteins should be considered as potential drug targets. Drugs interfering with this site such as mastoparan and related peptides, GPAnt-2 and suramin, are lead compounds in the design of selective G protein antagonists. Benzalkonium chloride and methoctramine have agonist or antagonist properties, depending on G protein subtypes. Such compounds would be very useful to delineate the functions of G proteins and G protein-coupled receptors, to understand some side effects of drugs used in therapy and to develop new therapeutic agents.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Complement C3a / chemistry
  • Complement C3a / metabolism
  • GTP-Binding Protein alpha Subunits, Gs / agonists
  • GTP-Binding Protein alpha Subunits, Gs / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Guanosine Triphosphate / metabolism
  • Hormones / chemistry
  • Hormones / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Neuropeptides / metabolism
  • Neurotransmitter Agents / metabolism*
  • Peptides
  • Polyamines / metabolism
  • Receptors, Drug / metabolism*
  • Signal Transduction / physiology
  • Wasp Venoms / chemistry
  • Wasp Venoms / metabolism*


  • Hormones
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • Peptides
  • Polyamines
  • Receptors, Drug
  • Wasp Venoms
  • mastoparan
  • Complement C3a
  • Guanosine Triphosphate
  • GTP-Binding Protein alpha Subunits, Gs