Partial postsynaptic 5-HT1A agonist properties of the novel stereoselective 8-OH-DPAT analogue (+)cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin, (+)ALK-3.
The present study assessed the pharmacological activity of the stereoisomers of the novel 8-OH-DPAT analogue cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin, ALK-3, at postsynaptic 5-HT1A receptors involved in 5-HT-mediated behaviour. Reserpine-pretreated rats were injected with (+)8-OH-DPAT (0.03-1.0 mg/kg s.c.), (+)ALK-3 (0.3-10.0 mg/kg s.c.) or (-)ALK-3 (3.0-10.0 mg/kg s.c.), and components of the '5-HT behavioural syndrome' were scored. (+8-OH-DPAT dose dependently elicited forepaw treading, flattened body posture and hindlimb abduction. In this respect, (+)ALK-3 was significantly less efficacious although its behavioural action was prevented by pindolol (8 mg/kg s.c.), indicating that it was 5-HT1A receptor mediated. Following pretreatment, (+)ALK-3 dose dependently, but partially, attenuated the effect of (+)8-OH-DPAT. (-)ALK-3 did not elicit 5-HT behaviours per se, and only very weakly antagonized the behavioural actions of (+)8-OH-DPAT at the highest dose tried. Our data indicate that the (+) enantiomer of ALK-3 is a partial but stereoselective agonist at postsynaptic 5-HT1A receptors.
Hjorth
S
S
MRC Unit, Radcliffe Infirmary, Oxford, England.
Sharp
T
T
Hacksell
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U
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C054003:8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine