piperidines and alaproclate

Although relatively few drugs that specifically influence serotonin neurons have been used in humans, a wide variety of drugs has been used to modify serotonergic function in experimental animals. Several classes of agents increase serotonergic function. These include serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) and monoamine oxidase inhibitors, which elevate serotonin stores; uptake inhibitors and releasers, which increase the concentration of serotonin in the synaptic cleft; and direct serotonin agonists, which mimic the action of serotonin on synaptic receptors. In addition, several kinds of drugs decrease serotonergic function, including serotonin depletors and agents that destroy serotonin neurons, as well as direct serotonin-receptor antagonists. The array of drugs now available improves the opportunities for clarifying the physiological roles of serotonin and gives promise of several therapeutic applications, including treatment of myoclonus.

Topics: Alanine; Brain; Citalopram; Clomipramine; Fenfluramine; Fluoxetine; Fluvoxamine; Humans; Monoamine Oxidase Inhibitors; Neurons; Oximes; p-Chloroamphetamine; Paroxetine; Piperidines; Propylamines; Receptors, Serotonin; Reserpine; Serotonin; Serotonin Antagonists; Synapses; Tetrabenazine; Zimeldine

Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.

Topics: 5-Hydroxytryptophan; Alanine; Citalopram; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Imipramine; Oximes; Paroxetine; Piperidines; Propylamines; Serotonin; Serotonin Antagonists; Trazodone; Zimeldine

This review concerns effects of stereoisomers on 5-HT uptake in brain tissue and/or blood platelets. All studies in which at least a pair of stereoisomers were used are considered. Differences between effects of stereoisomers of antidepressants as well as other drugs on 5-HT uptake are discussed. The findings indicate that 5-HT uptake is a stereoselective process. A topographical model of the 5-HT uptake area is proposed, based mainly on comparisons between spatial features of stereoisomers that inhibit 5-HT uptake.

Topics: Alanine; Amphetamine; Aniline Compounds; Animals; Antidepressive Agents; Blood Platelets; Brain; Fluoxetine; Humans; Male; Methadone; Mianserin; Mirtazapine; Morpholines; Naphthalenes; Nefopam; Nomifensine; Paroxetine; Piperidines; Rabbits; Serotonin; Stereoisomerism; Tranylcypromine; Viloxazine; Zimeldine

Topics: Alanine; Animals; Avoidance Learning; Memory; Mental Recall; Piperidines; Rats; Retention, Psychology; Serotonin; Synaptic Transmission

The potential stimulatory and inhibitory effects on female sexual behaviour of five 5HT antagonists and five agents that increase 5HT activity, were noted in ovariectomised rats primed with various steroid regimes such that they were either "receptive" (LQ greater than 50%) or "non-receptive" (LQ less than 50%). The 5HT antagonists cinanserin, mianserin, ketanserin and metergoline all inhibited behaviour in receptive rats. Methysergide and cinanserin stimulated behaviour in non-receptive rats. All the drugs which increased 5HTP activity, i.e., 5HTP, zimelidine, alaproclate, WY 26002 and quipazine stimulated sex behaviour in non-receptive rats. In rats that had been ovariectomised only, part of this effect was probably due to stimulation of adrenal progesterone, but a significant stimulatory effect could still be observed in ovariectomised-adrenalectomised rats. 5HT also had a significant inhibitory effect on receptive rats, and the other agonists showed a similar but non-significant tendency. In view of the fact that 4 out of 5 of the 5HT antagonists inhibited sexual behaviour, we hypothesise that 5HT has a stimulatory role in the control of female sexual behaviour. The possible mechanisms mediating the dual action of 5HTP on female sexual behaviour are discussed.

Topics: 5-Hydroxytryptophan; Adrenalectomy; Alanine; Animals; Castration; Cinanserin; Female; Ketanserin; Metergoline; Methysergide; Mianserin; Piperidines; Progesterone; Quipazine; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin; Sexual Behavior, Animal; Zimeldine