Abstract
Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol ≥ fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anden NE, Roos BE, Werdinius B (1964) Effect of chlorpromazine, haloperidol and reserpine on the levels of phenolic acid in rabbit corpus striatum. Life Sci 3:149–158
Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35:53–68
Bannon MJ, Reinhard JF Jr, Bunney EB, Roth RH (1982) Unique response to antipsychotic drugs is due to the absence of terminal autoreceptors in mesocortical dopamine neurons. Nature 296:444–446
Bannon MJ, Wolf ME, Roth RH (1983) Pharmacology of dopamine neurons innervating the pre-frontal, cingulate and piriform cortices. Eur J Pharmacol 92:119–125
Carlsson A, Lindqvist M (1963) Effect of chlorpromazine and haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol 20:945–957
Chang WH, Scheinin M, Burns RS, Linnoila M (1983) Rapid and simple determination of homovanillic acid in plasma using high performance liquid chromatography with electrochemical detection. Acta Pharmacol Toxicol 53:275–279
Chang WH, Yeh EK, Hu WH, Tseng YT, Chung MC, Chang HF (1986a) Acute and chronic effects of haloperidol on plasma and brain homovanillic acid in the rat. Biol Psychiatry 21:374–381
Chang WH, Yeh EK, Hu WH, Tseng YT, Chung MC, Chang HF (1986b) Pre-frontal cortex: possible site of antipsychotic action of haloperidol. Biol Psychiatry 21:422–424
Chang WH, Chen TY, Yeh EK (1987a) Time-response curves of homovanillic acid in caudate and pre-frontal cortex following acute neuroleptic administration. Psychopharmacology 93:403–404
Chang WH, Tseng YT, Yeh EK (1987b) Time course of homovanillic acid in rat brain regions and plasma following acute haloperidol administration. Chinese Psychiatry 1:183–188
Haase HJ (1978) The purely neuroleptic effects and its relation to the “neuroleptic threshold”. Acta Psychiatr Belg 78:19–36
Hollister LE (1983) Clinical pharmacology of psychotherapeutic drugs. Churchill Livingstone, New York
Jenner P, Clow A, Reavill C, Theodorou A, Marsdon CD (1980) Stereoselective actions of substituted benzamide drugs on cerebral dopamine mechanisms. J Pharm Pharmacol 32:39–44
Laduron P, DeBie K, Leysen J (1977) Specific effect of haloperidol on dopamine turnover in the frontal cortex. Naunyn-Schmiedeberg's Arch Pharmacol 296:183–185
Matsumoto T, Uchimura H, Hirano M, Kim JS, Yokoo H, Shimomura M, Nakahara T, Inoue K, Oomagari K (1983) Differential effects of acute and chronic administration of haloperidol on homovanillic acid levels in discrete dopaminergic areas of rat brain. Eur J Pharmacol 89:27–33
Nyback H, Sedvall G (1968) Effect of chlorpromazine on accumulation and disappearance of catecholamines formed from tyrosine-C14 in brain. J Pharmacol Exp Ther 162:294–301
Snyder SH, Banerjee SP, Yamamura HI, Greenberg D (1974) Drugs, neurotransmitters and schizophrenia. Science 184:1243–1253
Stanley M, Wilk S (1977) The effect of antipsychotic drugs and their clinically inactive analogs on dopamine metabolism. Eur J Pharmacol 44:293–302
Stawarz RJ, Hill H, Robinson SE, Setler P, Dingell JV, Sulser F (1975) On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain. Psychopharmacologia 43:125–130
Thierry AM, Blanc G, Sobel A, Stinus L, Glowinski J (1973) Dopaminergic terminals in the rat cortex. Science 182:499–501
Westerink BHC, Lejeune B, Korf J, Van Praag HM (1977) On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Eur J Pharmacol 42:179–190
Wiesel F-A, Sedvall G (1975) Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat. Eur J Pharmacol 30:364–367
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chang, WH., Chen, TY., Wu, HS. et al. Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies. Psychopharmacology 95, 459–462 (1988). https://doi.org/10.1007/BF00172955
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00172955