Atlas of Science

Abstract

inpatients treated with antipsychotics and valproate. As serum carnitine levels increased from 66.1±4.7µmol/L to 89.2±7.8µmol/L, the prolactin levels decreased from 52.2±8.4ng/ml to 33.7±6.6ng/ml. The ratio of prolactin levels at one month against baseline was significantly negatively correlated with the ratio of acylcarnitine/free carnitine levels at one month against baseline by using Spearman's correlation coefficient (r=-0.537, p=0.0319). L-carnitine attenuates antipsychotic-induced hyperprolactinemia in a concentration-dependent manner. L-carnitine turns into acety-L-carnitine in the body, which is an acetylated form of L-carnitine and most abundant naturally occurring derivative. According to the 13 C NMR study, acetyl-L-carnitine is incorporated into the carbon skeleton of the neurotransmitter gamma-aminobutyric acid (GABA). L-carnitine is used for GABA biosynthesis in the brain. GABA exerts a dual control on prolactin secretion, one excitatory mediated in part by the impairment of the tubero-infundibular dopaminergic (TIDA) system function, the other inhibitory occurring at the level of the anterior pituitary (Fig. 1). The two sites of action may be responsible for the excitatory and inhibitory effects of GABA on prolactin secretion. However, the former excitatory effect of GABA on prolactin secretion may not affect prolactin levels in patients with antipsychotic-induced hyperprolactinemia because TIDA system has been blocked by antipsychotics. Thus, the latter inhibitory effect of GABA on prolactin secretion may influence on prolactin levels, resulting in a mild prolactin sparing effect. Anterior pituitary GABA receptors have been shown to play a functional role in the inhibitory control of prolactin secretion. The inhibitory action of GABA seems to be mediated mainly by the activation of the high affinity receptor, which may appear in high proractin levels by suckling. Proactin lowering effect of GABA is a receptor-mediated event, where the high affinity receptor population is present. Scince antipsychotic-induced hyperprolactinemia may induce high affinity receptors like suckling, GABA reduces prolactin levels through pituitary GABA receptors (Fig. 1). Although the main physiological control of prolactin secretion is exerted by the inhibiting action of dopamine, anterior pituitary GABA receptors have been shown to play a functional role in the inhibitory control of prolactin secretion in schizophrenia patients with antipsychotic-induced hyperprolactinemia. L-carnitine attenuates antipsychotic-induced hyperprolactinemia by stimulating pituitary GABA receptors. This mechanism is irrelevant to the dopaminergic system, therefore psychotic symptoms may not be aggravated. Pituitary GABA receptor stimulation by L-carnitine may be a new strategy for antipsychotic-induced hyperprolactinemia.