Pilocarpine is mainly known as a drug for the treatment of glaucoma and it is also used as a stimulant of sweat and lachrymal glands. Species of the genus Pilocarpus are collectively named jaborandi in Brazil and their leaves are the only known source of this imidazole alkaloid. Pilocarpine is mainly obtained from two species, Pilocarpus microphyllus and Pilocarpus jaborandi and, despite the economical and pharmacological importance of this alkaloid, very little is known about pilocarpine, from basic information on the contents in different jaborandi species and plant tissues to the biosynthetic route and the metabolic control. This review will focus briefly on the genus jaborandi, then on what is known about pilocarpine biosynthesis followed by possible biotechnological applications aiming to produce the alkaloid in vitro. Finally, the alkaloids found in this genus, their plant sources and pharmacological applications will be reviewed. © 2010 Nova Science Publishers, Inc. 6380Abreu, I.N., Andreazza, N.L., Sawaya, A.C.H.F., Eberlin, M.N., Mazzafera, P., Cell suspension as a tool to study the biosynthesis of pilocarpine in Jaborandi (2007) Plant Biology, 9, pp. 793-799Abreu, I.N., Mazzafera, P., Eberlin, M.N., Zullo, M.A.T., Sawaya, A.C.H.F., Characterization of the variation of the imidazole alkaloid profile of Pilocarpus microphyllus in different seasons and parts of the plant by electrospray ionization mass spectrometry fingerprinting and identification of novel alkaloids by tandem mass spectrometry (2007) Rapid Commun. Mass Spectr, 21, pp. 1205-1213Abreu, I.N., Sawaya, A.C.H.F., Eberlin, M.N., Mazzafera, P., Production of pilocarpine in callus of Jaborandi (Pilocarpus microphyllus Stapf) (2005) Vitro Cellular Developmental Biology - PLANT, 41, pp. 806-811Andrade, P., Willoughby, R., Pomponi, S.A., Kerr, R.G., Biosynthetic studies of the alkaloid, stevensine, in a cell culture of the marine sponge Teichaxinella morchella (1999) Tetrahedron Letters, 40, pp. 4775-4778Andrade-Neto, M., Mendes, P.H., Silveira, E.R., An imidazole alkaloid and other constituents from Pilocarpus trachyllophus (1996) Phytochemistry, 42, pp. 885-887Andreazza, N.L., (2009) Transporte de pilocarpina em suspensões celulares de Pilocarpus microphyllus, , Universidade estadual de CampinasAndreazza, N.L., Abreu, I.N., Sawaya, A.C.H.F., Eberlin, M.N., Mazzafera, P., Production of imidazole alkaloids in cell cultures of jaborandi as affected by the medium pH (2008) Biotechnology Letters, 31, pp. 607-614Avancini, G., Abreu, I.N., Saldaña, M.D.A., Mohamed, R.S., Mazzafera, P., Induction of pilocarpine formation in jaborandi leaves by salicylic acid and methyljasmonate (2003) Phytochemistry, 63, pp. 171-175Baricevic, D., Umek, A., Kreft, S., Maticic, B., Zupancic, A., Effect of water stress and nitrogen fertilization on the content of hyoscyamine and scopolamine in the roots of deadly nightshade (Atropa belladonna) (1999) Environmental and Experimental Botany, 42, pp. 17-24Braun, M., Buhne, C., Cougali, D., Schaper, K., Frank, W., Convergent diasteroselective synthesis of isopilocarpine by one-pot Michael-addition-alkylation reaction (2004) Synthesis, 17, pp. 2905-2909Cordell, G.A., (1981) Introduction to alkaloids: a biogenetic approach, , New York, John Wiley & SonsDavies, S.G., Roberts, P.M., Stephenson, P.T., Thomson, J.E., Syntheses of the racemic jaborandi alkaloids pilocarpine, isopilocarpine and pilosinine (2009) Tetrahedron Letters, 50 (3127), pp. 3509-3512Davies, S.G., Robets, P.M., Stephenson, P.T., Storr, H.R., Thomson, J.E., A practical and scalable total synthesis of the jaborandi alkaloid (+)-pilocarpine (2009) Tetrahedon, 65, pp. 8283-8296de Luca, L., Naturally occurring and synthetic imidazoles. Their chemistry and their biological activities (2006) Current Medical Chemistry, 13, pp. 1-23Dewick, P.M., (1997) Medicinal natural products: a biosynthetic approach, , New York, John Wiley & SonsGerard, A.W., Alkaloid and active principles of jaborandi (1875) Pharmaceutical Journal, 5, p. 865Godoy-Hernandez, G.C., Vazquez-Flota, F.A., Loyola-Vargas, V.M., The exposure to trans-cinnamic acid of osmotically stressed Catharanthus roseus cells cultured in a 14-L bioreactor increases alkaloid accumulation (2000) Biotechnology Letters, 22, pp. 921-925Goodman, L.S., Gilman, A., (2001) The pharmacological basis of therapeutics, , 10th edition, New York, McGraw Hill Companies IncHardy, M.E., Sur le jaborandi (Pilocarpus pinnatus) (1875) Bulletin Societe Chimi Paris, 24, pp. 497-500Hemscheidt, T., Spenser, I.D., Biosynthesis of anosmine, an imidazólico alkaloid of the orchid Dendrobium parishii (1991) Journal of Chemical Society - Chemical Communications, 7, pp. 494-497Hill, R.K., Barcza, S., Sterochemistry of the Jaborandi alkaloids (1966) Tetrahedon, 22, pp. 2889-2893Holmstead, B., Wassen, S.H., Schultes, R.E., Jaborandi: an interdisciplinary appraisal (1979) Journal of Ethnopharmacology, 1, pp. 3-21(1992) Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis., pp. 870-872. , IBAMA, Portaria n° 06N, Diário Oficial, Brasília, janeiro 15, 1992Joseph, C.J., Revisão sistemática do gênero Pilocarpus (ssp. brasileiras) (1967) Mecânica Popular, pp. 1-9. , OctoberKaastra, R.C., (1982) Pilocarpinae. Flora Neotropica. Monograph number 33, , New York Botanical Garden, New YorkLi, Z.H., Liu, Z.J., Effect of NaCl on growth, morphology, and camptothecin accumulation in Camptotheca acuminata seedlings (2003) Canadian Journal of Plant Science, 83, pp. 931-938Link, H., Bernauer, K., Über die Synthese der Pilocarpus-alkloide isopilosin und pilocarpin, sowie die absolute konfiguration dês (+)- Isopilosins (1972) Helvetica Chimica Acta, 55, pp. 1053-1062Link, H., Bernauer, K., Oberhans, W.E., Configuration of Pilocarpus alkaloids (1974) Helvetica Chimica Acta, 57, pp. 2199-2200Lucio, E.M.R., Rosalen, P.L., Sharapin, N., Souza-Brito, A.R.M., Avaliação toxicológica e screening hipocrático de epiisopilosine, alcalóide secundário de Pilocarpus microphyllus Staph (2000) Revista Brasileira de Farmacognosia, 9, pp. 23-35Lucio, E.M.R., Sharapin, N., França, H.S., Estudo de alcalóides de Pilocarpus pennatifolius Lemaire (2002) Revista Brasileira de Farmacognosia, 12, pp. 130-131Merbel, N.C., Tinke, A.P., Oosterhuris, B., Jonkman, J.H.G., Bohle, J.F., Determination of pilocarpine, isopilocarpine, pilocarpic acid and isopilocarpic aid in human plasma and urine by high performance liquid chromatography and tandem spectrometric detection (1998) Journal of Chromatography B, 708, pp. 103-112Oksman-Caldentey, K.M., Inze, D., Plant cell factories in the post-genomic era: New ways to produce designer secondary metabolites (2004) Trends in Plant Science, 9, pp. 433-440Oliveira, P.D., (2007) Filogenética de Pilocarpinae (Rutaceae), , PhD Thesis, Universidade de São PauloPark, R., On the use of Jaborandi or pilocarpine in the collapse of scarlatina maligna (1883) Lancet, 121, p. 1041Payo Hill, A., Dominicis, M.E., Oquendo, M., Sarduy, R., Obtención de pilocarpina a partir de Pilocarpus racemosus Vahl (1995) Revista Cubana de Farmacia, 29, pp. 123-125Pinheiro, C.U.B., Jaborandi (Pilocarpus sp., Tutaceae): a wild species and its rapid transformation into a crop (1997) Econ. Bot, 51, pp. 49-58Pinheiro, C.U.B., Extrativismo, cultivo e privatização do jaborandi (Pilocarpus microphyllus Stapf ex Holm.Rutaceae) no Maranhão (2002) Acta bot. bras, 16, pp. 141-150Rastogi, N., Abaul, J., Goh, K.S., Devallois, A., Philogene, E., Bourgeois, P., Antimycobacterial activity of chemically defined natural substances form the Caribbean flora in Guadeloupe (1998) FEMS Immunology and Medical Microbiology, 20, pp. 267-273Sandhu, S.S., Abreu, I.N., Colombo, C.A., Mazzafera, P., Pilocarpine content and molecular diversity in Jaborandi (2005) Scientia Agricola, 63, pp. 478-482Santos, A.P., Moreno, P.R.H., Pilocarpus spp.: A survey of its chemical constituents and Biological activities (2004) Brazilian Journal of Pharmaceutical Sciences, 40, pp. 115-137Sawaya, A.C.H.F., Abreu, I.N., Andreazza, N.L., Eberlin, M.N., Mazzafera, P., HPLC-ESI-MS/MS of imidazole alkaloids in Pilocarpus microphyllus (2008) Molecules, 13, pp. 1518-1529Sawaya, A.C.H.F., Gontijo Vaz, B., Eberlin, M.N., Mazzafera, P., (2010) Comparative study of imidazole alkaloids in seven species of Pilocarpus, , SubmmitedSkorupa, L.A., (1996) Revisão Taxonômica de Pilocarpus Vahl (Rutaceae), , PhD Thesis, Universidade de São PAuloSousa, M.P., Matos, M.E.O., Matos, F.J.A., Machado, M.I.L., Craveiro, A.A., (1991) Constituintes químicos ativos de plantas medicinais brasileiras, , Fortaleza, Brazil, Editora da Universidade Federal do CearáSouza, R.C., Fernandes, J.B., Vieira, P.C., Silva, M.F.G.F., Godoy, M.F.P., Pagnocca, F.C., Bueno, O.C., Pirani, J.R., New imidazole alkaloid and other constituents from Pilocarpus grandiflorus and their antifungal activity (2005) Zeitschrift für Naturforschung B, 60, pp. 787-791Stafford, A., Morris, P., Fowler, M.W., Plant cell biotechnology: a perpective (1986) Enzyme Microbial Technology, 8, pp. 578-587Superintendência do Desenvolvimento do Maranhão (1970) Novo Zoneamento do Estado do Maranhão, , SUDEMA, São Luis, MATedeschi, E., Kamionsky, J., Zeider, D., Fackler, S., Isolation, characterization, and synthesis of trans-pilosine stereoisomers occurring in nature Circular dicrooism and mass spectral studies (1974) Journal of Organic Chemistry, 39, pp. 1864-1879Uva, L., Librizzi, L., Marchi, N., Noe, F., Bongiovammi, R., Vezzani, A., Janigro, D., de Curtis, M., Acute induction of epilelptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability (2008) Neuroscience, 151, pp. 303-312Valdez, I.H., Wolff, A., Atkinson, J.C., Macynsky, A.A., Foz, P.C., Use of pilocarpine during head and neck radiation therapy to reduce xerostomia and salivary dysfunction (1993) Cancer, 71, pp. 1848-1851Van der Fits, L., Zhang, H., Menke, F.L.H., Deneka, M., Memelink, J., A Catharanthus roseus BPF-1 homologue interacts with an elicitor-responsive region of the secondary metabolite biosynthetic gene Str and is induced by elicitor via a JA-independent signal transduction pathway (2000) Plant Molecular Biology, 44, pp. 675-685Verpoorte, R., Memelink, J., Engeneering secondary metabolite in plant (2002) Current Opinion in Biotechnology, 13, pp. 181-187Verpoorte, R., v.d.H., R., Schripsema, J., Hoge, J.H.C., Ten Hoopen, H.J.G., Plant cell biotechnology for the production of alkaloids: Present status and prospects (1993) Journal of Natural Products, 56, pp. 186-207Verpoorte, R., vanderHeijden, R., tenHoopen, H.J.G., Memelink, J., Metabolic engineering of plant secondary metabolite pathways for the production of fine chemicals (1999) Biotechnology Letters, 21, pp. 467-479Vieira, R.F., Conservation of medicinal and aromatic plants in Brazil (1999) Perspectives on new crops and new uses, pp. 152-159. , Janick, J., Alexandria, ASHS PressVoigtlander, H.W., Balsam, G., Engelhardt, M., Epiisopiloturin, ein Neues Pilocapus-Alkaloid (1978) Archiv der Pharmazie, 311, pp. 927-935