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J Pharmacol Exp Ther. 1983 Jan;224(1):21-7.
Effect of yohimbine on rat prolactin secretion.

Meltzer HY, Simonovic M, Gudelsky GA.

It was recently proposed that yohimbine (YOH), an indole alkaloid with multiple pharmacological effects, is an antagonist of the D2 dopamine (DA) receptor. Because the pituitary DA receptor involved in the inhibition of prolactin (PRL) secretion is the prototypic D2 receptor, we examined the effect of YOH on PRL secretion in male rats. YOH produced marked, dose-dependent and sustained increases in plasma PRL levels. However, YOH did not block the inhibitory effect of DA on PRL release from rat pituitary glands in vitro, did not displace [3H]spiperone from bovine pituitary membranes and had no effect on the concentration of DA in pituitary stalk plasma of anesthetized rats, suggesting that the stimulation of PRL release by YOH is not due to its antidopaminergic effects. Clonidine, an alpha-2 adrenergic agonist, produced a partial, non-dose-dependent inhibition of the YOH-induced rise in serum PRL levels. Two antagonists of the H1 histamine receptor, diphenhydramine and promethazine, markedly antagonized the PRL-releasing effect of YOH, but another H1 blocker, chlorpheniramine, and an H2 antagonist, metiamide, had no effect. Serotonin receptor blockers, cyproheptadine, mianserin and pizotifen, and the opiate antagonist, naloxone, also had no effect on the PRL response to YOH. Nevertheless, the PRL-releasing effect of YOH was potentiated 24 hr after the administration of reserpine or para-chlorophenylalanine, an inhibitor of serotonin synthesis. Thus, the mechanisms by which YOH stimulates rat PRL secretion has has not been fully elucidated. It is possible that YOH may stimulate PRL secretion by a novel mechanism, possibly through the intervention of a PRL-releasing factor.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6294278&dopt=Abstract




Psychopharmacology (Berl). 1983;79(4):372-4.
Effects of L-histidine and promethazine on apomorphine and amantadine stereotypy in rats.

Balsara JJ, Dhavare BS, Nandal NV, Chandorkar AG.

Pretreatment with L-histidine, a precursor of brain histamine, and promethazine, a H1 receptor blocker, failed to modify apomorphine-induced stereotyped behaviour in rats. In contrast, pretreatment with L-histidine significantly decreased the intensity of amantadine stereotypy while pretreatment with promethazine significantly increased the intensity of amantadine stereotypy in rats. The results suggest that drugs which influence central histaminergic mechanisms are effective only in modifying the stereotyped behaviour induced by the indirectly-acting DA agonist amantadine, and fail to modify the stereotyped behaviour induced by apomorphine, a directly-acting DA agonist.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6407056&dopt=Abstract




Pharmazie. 1981 Dec;36(12):815-8.
[Metabolic interactions of promethazine (author's transl)]

[Article in German]

Pfeifer S, Borchert HH, Schuster S, Schulz H.

Owing to enzyme induction, the pretreatment of female Wistar rats with promethazine (Prothazin, Atosil) produces a shortening of the hexobarbital sleeping time, a slight increase in the relative liver weight, an increase in the N-demethylation of aminophenazone, the O-demethylation of codeine phosphate, the O-demethylation of p-nitroanisol, the glucuronidation of p-nitrophenol and the NADPH-cytochrome c reductase activity in the 9.000 g supernatant of liver homogenates. Particularly striking are the strong stimulation of the N-demethylation and the also potentiated [in contrast to the findings obtained with dioxopromethazine (Prothanon)] UDP-glucuronyltransferase activity, whereas the cytochrome P-450 concentration shows a slight trend toward increase, but this is not statistically significant. The findings obtained justify the expectation of drug interactions in case of repeated application of promethazine in the framework of a combined therapy.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6799969&dopt=Abstract













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