Isoteoline, a putative serotonin antagonist, inhibits meta -chlorophenylpiperazine, but not 1-(2, -dimethoxy-4-iodphenyl)-2-aminopropane and 8-hydroxy-2-(di-n-propylamino)-tetraline-induced increase of serum prolactin levels.
Serotonin, in addition to dopamine and other factors, is known to participate in the control of prolactin (PRL) and gonadotropins secretion. Isoteoline (IST), a putative serotonin antagonist and dopamine agonist, was studied for its neuroendocrine effects on PRL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). IST was given intraperitoneally to adult male rats at doses of 0.25, 1 and 4 mg kg(-1)alone and 30 min prior to the injection of three 5-HT agonists with preferential affinity for various receptor subtypes: meta -chlorophenylpiperazine (m CPP) for 5-HT2C; 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) for 5-HT2A and 8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) for 5-HT1A. m CPP (2.5 mg kg(-1)), DOI (2.5 mg kg(-1)) and 8-OH-DPAT (1 mg kg(-1)) increased the serum PRL levels to a similar value, without affecting FSH and LH concentrations. IST by itself modified neither PRL nor gonadotropins serum levels. IST antagonized the m CPP-induced elevation in serum PRL, the lowest dose being the most effective. It had no effect on DOI and 8-OH-DPAT-induced increases of PRL levels and produced no significant changes in the gonadotropins levels when used as an antagonist. The results are discussed in terms of the likely involvement of serotonin vs dopamine mechanism in the effect of IST. It is concluded that the inhibition of the m CPP-induced rise of PRL levels by IST confirmed the serotonin antagonistic activity, previously demonstrated for this compound in other studies. The present results are also suggestive of possible selectivity of this antagonism of IST for the 5-HT2C vs 5-HT2A and 5-HT1A receptors, all of which are involved in the control of PRL secretion.
Zhelyazkova-Savova
M D
MD
Department of Preclinical and Clinical Pharmacology, Varna Medical University, Bulgaria.
Negrev
N
N
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors*; D000662:Amphetamines / Q000037:antagonists & inhibitors*; D000818:Animals; D001060:Aporphines / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010879:Piperazines / Q000037:antagonists & inhibitors*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000662:Amphetamines; D001060:Aporphines; D010879:Piperazines; D012702:Serotonin Antagonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C044170:isoteolin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine