Potent anorexic-like effects of RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane) in the rat: a comparison with other dopamine-receptor agonists.
Modification of food intake and motor activity was investigated following administration of amphetamine (AMP), apomorphine (APO) and three novel 2-aminoindanes (2-AI): 2-di-n-propylaminoindane (JPC-60-36), 2-di-n-propylamino-5,6-dimethoxyindane (JPC-211) and 2-di-n-propylamine-4,7-dimethoxyindane (RDS-127). These compounds demonstrated dose- and time-related inhibition of food intake in male rats which were habituated to eating 4 hr each day. The ranked potencies were as follows: RDS-127 greater than AMP = APO greater than JPC-60-36 and JPC-211 was inactive. 2-di-n-Propylamine-4,7-dimethoxyindane (RDS-127) did not increase motor activity in a dose range that Significantly inhibited food intake (66% of control intake with 0.08 mumol/kg). Food intake inhibition was blocked by pimozide, but not by propranolol or phentolamine. The anorectic-like actions of RDS-127 were long-lasting (greater than 4 hr) and RDS-127 was approximately 3-fold more potent than amphetamine or apomorphine in producing increased locomotor activity; the other 2-aminoindanes were less potent in producing hyperactivity. Hyperactivity responses were blocked by pimozide, but not by alpha-methyl-p-tyrosine. These results suggest that 2-aminoindanes may modify motor behaviors, at least in part, via direct stimulation of dopamine receptors. The structure-activity relationships of 2-aminoindanes on locomotor activity and inhibition of food intake are discussed.
D000818:Animals; D000855:Anorexia / Q000503:physiopathology; D001058:Apomorphine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D002149:Energy Intake; D005247:Feeding Behavior / Q000187:drug effects*; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*
D007189:Indans; D007192:Indenes; D011954:Receptors, Dopamine; C036172:2-di-n-propylaminoindan; C035604:2-N,N-di-n-propylamino-4,7-dimethoxyindan; D001058:Apomorphine; D003913:Dextroamphetamine