ORIGINAL PAPER Comparative extrapyramidal effects of Rauwolfia vomitoria, chlorpromazine and reserpine in mice Sunday Agba Bisong • Richard Earl Brown • Eme Effiom Osim Received: 21 November 2011 / Accepted: 1 March 2012 / Published online: 30 March 2012 Ó The Japanese Society of Pharmacognosy and Springer 2012 Abstract Most antipsychotics interfere with the dopami- nergic system, resulting in extrapyramidal effects. This study compared the extrapyramidal effects of chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res), used as antipsychotics, in mice. Ninety age- matched male CD-1 strain of mice (25–33 g body weight) were divided into 3 groups, each consisting of 5 subgroups (n = 6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before testing. Locomotor behaviour (open field test) and motor coordination (acceleratory rotarod) were assessed. Mice were also observed for 10 min for tremor and vacuous chewing movement (VCM). CPZ and Res dose- dependently decreased locomotor behaviour and impaired motor coordination (p \ 0.01). RV also decreased locomotor behaviour (4.0 mg/kg; p \ 0.05) but had minimal effect on motor coordination. VCM was lower in the RV group (0.17 ± 0.16/10 min) than the Res (6.8 ± 1.36/10 min) and Cpz groups (7.83 ± 1.95/10 min): F (4,25) = 10.703; p \ 0.01. The frequency of bouts of tremor was also lower in the RV group (1.17 ± 0.72/10 min) than the Res (21.2 ± 5.63/10 min) and Cpz (7.83 ± 1.59/10 min) groups: F (4,25) = 11.012; p \ 0.001. The root bark extract of R. vomitoria, therefore, has great potential in the management of psychotic disorders. Keywords Chlorpromazine Á Rauwolfia vomitoria Á Reserpine Á Extrapyramidal effects Introduction Treatment of psychotic disorders (schizophrenia and the manic phase of bipolar disorder as well as amphetamine- induced psychoses) using phenothiazine-derived first-gen- eration (typical) anti-psychotics such as chlorpromazine has been associated with extrapyramidal effects [1]. This was shown in a human population-based study in Xhosa in the Eastern Cape of South Africa with a high prevalence of cases of tardive dyskinesia in psychiatric patients treated with chlorpromazine and other first-generation typical antipsychotic drugs [2]. It was also reported in rats which received chronic administration of chlorpromazine (5 mg/ kg), showing a decrease in extracellular dopamine, nor- adrenaline and serotonin levels and a significant increase in orofacial hyperkinetic movements, which are hallmarks of extrapyramidal side effects [3]. The other phenothiazines which have higher potency than chlorpromazine, but pos- sess a higher degree of extrapyramidal side effects, are fluphenazine and haloperidol [4, 5]. These extrapyramidal effects occur via interference with dopamine receptors. Chlorpromazine is a strong antagonist of D2 dopamine receptors and a fairly strong antagonist of D1, D3 and D5 receptors [6–8]. Blocking of cortical dopamine receptors leads to extrapyramidal syndromes, such as tardive dyskinesia, dystonias and choreiform or dystonic form movements and tremor [9]. Despite these effects, chlorpromazine remains a commonly used and readily available standard antipsychotic drug [10], listed as one of the most essential drugs by the World Health Organization in 2003 [11]. S. A. Bisong Á E. E. Osim Department of Physiology, College of Medical Sciences, University of Calabar, Calabar PMB 1115, Nigeria S. A. Bisong (&) Á R. E. Brown Department of Psychology and Neuroscience, Dalhousie University, Life Science Building, Halifax, NS B3H 4R2, Canada e-mail: bisongsa@yahoo.com 123 J Nat Med (2013) 67:107–112 DOI 10.1007/s11418-012-0657-8