Dimethylhomotryptamine (DMHT; developmental code name U-6056), also known as N,N-dimethylhomotryptamine or as 3-[3-(dimethylamino)propyl]indole, is a homotryptamine and homologue of the psychedelic tryptamine dimethyltryptamine (DMT) in which the alkyl side chain has been lengthened by one carbon atom. The homologue of DMT in which the alkyl side chain has been shortened by one carbon atom is gramine (3-(N,N-dimethylaminomethyl)indole).

Use and effects

According to Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved) and other publications, DMHT was studied by the Upjohn Company under the code name U-6056. It was assessed in a clinical study of 10individuals at doses of up to 10mg by intravenous injection and 70mg by intramuscular injection, but produced no psychoactive or hallucinogenic effects besides mild agitation or anxiety and caused slight increases in heart rate and blood pressure. For comparison, DMT has been reported to produce psychedelic effects at doses as low as 20 to 50mg by intramuscular injection. The human properties and effects of the lower homologue gramine are unknown.

Pharmacology

Pharmacodynamics

DMHT showed the same affinity for serotonin receptors in the rat fundus strip as dimethyltryptamine (DMT) (A2 = 1,000nM and 1,000nM, respectively). It also shows low affinity for the serotonin 5-HT3 receptor (Ki = 730nM). The drug's analogue homotryptamine (the N,N-didesmethyl analogue) showed about 5- to 10-fold lower potency than tryptamine and DMT as a serotonin receptor agonist in the rat uterus and stomach strip and showed abolished affinity for the serotonin 5-HT1E and 5-HT1F receptors (Ki = >10,000nM). DMHT is a potent serotonin reuptake inhibitor (SRI), with an affinity (IC50Tooltip half-maximal inhibitory concentration) for the serotonin transporter (SERT) of 58nM. It produced hyperthermia in rabbits.

Chemistry

Synthesis

The chemical synthesis of DMHT has been described.

Analogues

Homotryptamine.

DMHT's N,N-didesmethyl analogue is homotryptamine. Other DMT and DMHT homologues with further extended alkyl side chains have been studied, but were said to have no interesting activity. The highly potent selective serotonin reuptake inhibitor (SSRI) BMS-505130 (Ki = 0.18nM for the SERT) was derived via structural modification of DMHT. Gramine is an analogue of DMT and DMHT with a shortened alkyl side chain.

History

DMHT was first described in the scientific literature by William J. Turner and Sidney Merlis in 1959.

See also

External links