The Nature of the Binding Between LSD and a 5-HT Receptor: a Possible Explanation for Hallucinogenic Activity

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1974 Jun 1

PMID 4375525

Citations 5

Authors

M J Berridge

W T Prince

Affiliations

Soon will be listed here.

Abstract

1 (+)-Lysergic acid diethylamide (LSD) mimicked 5-hydroxytryptamine (5-HT) in its ability to stimulate fluid secretion, to change transepithelial and intracellular potentials as well as to increase the cyclic 3',5'-adenosine monophosphate (cyclic AMP) concentrations of isolated salivary glands of Calliphora.2 Unlike 5-HT, LSD disengages slowly from the receptor and fluid secretion continues despite repeated washing.3 Both 5-HT and tryptamine prevented LSD from acting on the glands.4 LSD bound to the receptor was slowly displaced when glands were treated with agonists (tryptamine) or antagonists (gramine).5 The property of LSD which permits it to function as an agonist despite remaining tightly bound to the receptor is discussed as a possible basis for its profound effects within the central nervous system.

Citing Articles

N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function.

Barker S Front Neurosci. 2018; 12:536.

PMID: 30127713 PMC: 6088236. DOI: 10.3389/fnins.2018.00536.

Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes.

Camicia F, Celentano A, Johns M, Chan J, Maldonado L, Vaca H PLoS Negl Trop Dis. 2018; 12(2):e0006267.

PMID: 29425245 PMC: 5823469. DOI: 10.1371/journal.pntd.0006267.

Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

Schindler E, Harvey J, Aloyo V Brain Res. 2012; 1491:98-108.

PMID: 23123701 PMC: 3559188. DOI: 10.1016/j.brainres.2012.10.057.

Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD).

Schindler E, Dave K, Smolock E, Aloyo V, Harvey J Pharmacol Biochem Behav. 2011; 101(1):69-76.

PMID: 22197710 PMC: 3272148. DOI: 10.1016/j.pbb.2011.12.002.

Vasopressin-like effects of psychotropic drugs in amphibian epithelia.

Grosso A, de Sousa R J Membr Biol. 1978; 40 Spec No:305-21.

PMID: 104041 DOI: 10.1007/BF02026013.

References

Berridge M, Prince W . Transepithelial potential changes during stimulation of isolated salivary glands with 5-hydroxytryptamine and cyclic AMP. J Exp Biol. 1972; 56(1):139-53. DOI: 10.1242/jeb.56.1.139. View

Gaddum J . Serotonin-LSD interactions. Ann N Y Acad Sci. 1957; 66(3):643-7; discussion, 647-8. DOI: 10.1111/j.1749-6632.1957.tb40754.x. View

Boakes R, Bradley P, Briggs I, Dray A . Antagonism of 5-hydroxytryptamine by LSD 25 in the central nervous system: a possible neuronal basis for the actions of LSD 25. Br J Pharmacol. 1970; 40(2):202-18. PMC: 1702892. DOI: 10.1111/j.1476-5381.1970.tb09914.x. View

WOOLLEY D, Shaw E . Evidence for the participation of serotonin in mental processes. Ann N Y Acad Sci. 1957; 66(3):649-65; discussion, 665-7. DOI: 10.1111/j.1749-6632.1957.tb40755.x. View

Baker R, Chothia C, Pauling P, Weber H . Molecular structures of hallucinogenic substances: lysergic acid diethylamide, psilocybin, and 2,4,5-trimethoxyamphetamine. Mol Pharmacol. 1973; 9(1):23-32. View

Berridge M, Prince W . Mode of action of hallucinogenic molecules. Nat New Biol. 1973; 243(130):283-4. DOI: 10.1038/newbio243283a0. View

Aghajanian G . Influence of drugs on the firing of serotonin-containing neurons in brain. Fed Proc. 1972; 31(1):91-6. View

Bradley P . Synaptic transmission in the central nervous system and its relevance for drug action. Int Rev Neurobiol. 1968; 11:1-56. DOI: 10.1016/s0074-7742(08)60383-9. View

MANSOUR T, SUTHERLAND E, RALL T, Bueding E . The effect of serotonin (5-hydroxytryptamine) on the formation of adenosine 3',5'-phosphate by tissue particles from the liver fluke, Fasciola hepatica. J Biol Chem. 1960; 235:466-70. View

10.

Prince W, Berridge M, Rasmussen H . Role of calcium and adenosine-3':5'-cyclic monophosphate in controlling fly salivary gland secretion. Proc Natl Acad Sci U S A. 1972; 69(3):553-7. PMC: 426505. DOI: 10.1073/pnas.69.3.553. View

11.

Marchbanks R . Serotonin binding to nerve ending particles and other preparations from rat brain. J Neurochem. 1966; 13(12):1481-93. DOI: 10.1111/j.1471-4159.1966.tb04309.x. View

12.

Greenberg M . Structure-activity relationship of tryptamine analogues on the heart of Venus mercenaria. Br J Pharmacol Chemother. 1960; 15:375-88. PMC: 1481859. DOI: 10.1111/j.1476-5381.1960.tb01260.x. View

13.

Berridge M . The mode of action of 5-hydroxytryptamine. J Exp Biol. 1972; 56(2):311-21. DOI: 10.1242/jeb.56.2.311. View

14.

Kang S, Green J . Steric and electronic relationships among some hallucinogenic compounds. Proc Natl Acad Sci U S A. 1970; 67(1):62-7. PMC: 283167. DOI: 10.1073/pnas.67.1.62. View

15.

Berridge M, Patel N . Insect salivary glands: stimulation of fluid secretion by 5-hydroxytryptamine and adenosine-3',5'-monophosphate. Science. 1968; 162(3852):462-3. DOI: 10.1126/science.162.3852.462. View

16.

Tebecis A, Di Maria A . A re-evaluation of the mode of action of 5-hydroxytryptamine on lateral geniculate neurones: comparison with catecholamines and LSD. Exp Brain Res. 1972; 14(5):480-93. DOI: 10.1007/BF00236590. View

17.

Chothia C, Pauling P . On the conformations of hallucinogenic molecules and their correlation. Proc Natl Acad Sci U S A. 1969; 63(4):1063-70. PMC: 223427. DOI: 10.1073/pnas.63.4.1063. View

18.

Van Vunakis H, Farrow J, Gjika H, Levine L . Specificity of the antibody receptor site to D-lysergamide: model of a physiological receptor for lysergic acid diethylamide. Proc Natl Acad Sci U S A. 1971; 68(7):1483-7. PMC: 389223. DOI: 10.1073/pnas.68.7.1483. View

19.

McCoy A, Welsh J . Actions of dlysergic acid diethylamide and its 2-bromo derivative on heart of Venus mercenaria. Science. 1957; 125(3243):348. DOI: 10.1126/science.125.3243.348. View

20.

Berridge M . The role of 5-hydroxytryptamine and cyclic AMP in the control of fluid secretion by isolated salivary glands. J Exp Biol. 1970; 53(1):171-86. DOI: 10.1242/jeb.53.1.171. View