Guanidine is a small basic compound. Guanidine stimulates the neuromuscular junction presynaptically by inhibiting voltage-gated potassium (Kv) channels, leading to the enhanced release of acetylcholine in the synaptic cleft. This stimulatory effect of guanidine underlies its use in the therapy for the neuromuscular diseases. The hydrochloride salt of guanidine was approved by FDA for the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert.

Guanidine is a small basic compound. Guanidine stimulates the neuromuscular junction presynaptically by inhibiting voltage-gated potassium (Kv) channels, leading to the enhanced release of acetylcholine in the synaptic cleft. This stimulatory effect of guanidine underlies its use in the therapy for the neuromuscular diseases. The hydrochloride salt of guanidine was approved by FDA for the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert.

Robenidine (l,3-6ts (p-chlorobenzylidenamino) guanidine hydrochloride) is an effective anticoccidial, first introduced by Kantor, Kennett, Waletzky & Tomcufcik (1970). It does not affect the earliest stages in the coccidial life-cycle and its main activity is against the almost mature first generation schizont. It is used as an aid in the prevention of coccidiosis caused by Eimeria mivati, E. brunetti, E. tenella, E. acervulina, E. maxima and E. necatrix in broiler chickens.

Pimagedine is a nucleophilic hydrazine. It was shown to inhibit diamine oxidase (histaminase), which catalyzes the oxidative deamination of diamines histamine and putrescine. Pimagedine was also reported to inhibit nitric oxide synthase (NOS) based on its structural similarity to the NOS substrate L-arginine. Although pimagedine affects constitutive NOS (cNOS) isoform, it has been demonstrated to be a relatively selective inhibitor of the inducible NOS (iNOS) isoform. Pimagedine was shown to stabilize S-adenosylmethionine decarboxylase (SAMDC). Pimagedine (aminoguanidine HCl) has been shown to be an effective agent in reducing the severity of the structural and functional alterations associated with experimental diabetic nephropathy. But clinical trial of pimagedine to prevent progression of diabetic nephropathy was terminated early due to safety concerns and apparent lack of efficacy.

Mitoguazone is a guanylhydrazone derivative with potential antineoplastic activity. Mitoguazone inhibits S-adenosyl-L-methionine decarboxylase (SAMD), an enzyme involved in the synthesis of polyamines, resulting in a decreased proliferation of tumor cells, antimitochondrial effects, and p53-independent apoptosis. In the 1960s the drug was investigated in clinical trials. Despite the responses in acute leukemia, chronic myelogenous leukemia, lymphoma, multiple myeloma, head and neck cancer, esophageal cancer and other types of cancer, the development of the drug was discontinued because of marked myelosuppression and mucositis. Using a weekly schedule of administration, mitoguazone had minimal toxicity and showed limited activity in patients with lymphoma, esophageal cancer, prostate cancer, and other types of tumors.

Mitoguazone is a guanylhydrazone derivative with potential antineoplastic activity. Mitoguazone inhibits S-adenosyl-L-methionine decarboxylase (SAMD), an enzyme involved in the synthesis of polyamines, resulting in a decreased proliferation of tumor cells, antimitochondrial effects, and p53-independent apoptosis. In the 1960s the drug was investigated in clinical trials. Despite the responses in acute leukemia, chronic myelogenous leukemia, lymphoma, multiple myeloma, head and neck cancer, esophageal cancer and other types of cancer, the development of the drug was discontinued because of marked myelosuppression and mucositis. Using a weekly schedule of administration, mitoguazone had minimal toxicity and showed limited activity in patients with lymphoma, esophageal cancer, prostate cancer, and other types of tumors.

Creatinolfosfate (or creatinol-O-phosphate, or COP) possesses anti-ischemic and anti-arrhythmic activities associated with improved ionic balance and heart performance. This compound exerts its cardioprotective effect by action on anaerobic glycolysis. The results of the toxicological studies showed that creatinolfosfate didn’t have side effects.

Guanazodine is a new antihypertensive drug. Guanazodine caused a sustained decrease in the systemic blood pressure of spontaneously hypertensive rats, renal hypertensive dogs and normal cats. No tachyphylaxis developed when the drug was administered orally. The heart rate decreased. Guanazodine relaxed the cat nictitating membrane, attenuated the positive chronotropic response to sympathetic nerve stimulation in anesthetized dogs and in isolated rabbit aorta to transmural electrical stimulation. Guanazodine potentiated the pressor response to noradrenaline but attenuated the response to tyramine in anesthetized cats. It may be concluded that the hypotensive effect of guanazodine is related to adrenergic neuron blocking action, the noradrenaline-depleting action in peripheral tissues is similar to the effect of guanethidine and bethanidine. However, this drug is less potent than guanethidine. Toxicity and side effects appear to be less with guanazodine than with guanethidine and bethanidine.

Adrenochrome monoaminoguanidine (S-Adchnon) is a hemostatic capillary-stabilizing agent demonstrating pharmacological effects against radiation injury by reducing side effects of radiation therapy on hematopoietic organ. Synthesized by a dehydrating reaction of adrenochrome and aminoguanidine it has superior properties than adrenochrome, an oxidation product of adrenalin remarkable for its efficiency as a haemostatic agent at very small doses and for its more rapid and equally intense action than that of adrenalin. Adrenochrome does not alter the cardiac rhythm and does not cause any hypertension or internal haemorrhages and would be suitable for therapeutic applications, however, its instability, in aqueous or alcoholic solution, makes its use substantially impossible. S-Adchnon was devised, approved by the Japanese Ministry of Health, Labor and Welfare in 1962 and used widely in Japan. Adrenochrome monoaminoguanidine has negligible toxicity, stable and could be made into salts for aqueous dosage, especially for injection. Adrenochrome monoaminoguanidine methanesulfonate (AMM) enhances the recovery from radiation-induced leukopenia in rabbits and in humans, and inhibits the increases in chromosome aberrations in peripheral lymphocytes of patients with cervical carcinoma under radiotherapy. It has been shown that the radiation-induced initial decrease in number of peripheral blood leukocytes (PBL) is not affected by AMM, but recovery from the decrease is enhanced, shortening the period of leukopenia. This suggests that AMM may not exert its effects by protecting PBL directly but by protecting stem and/or progenitor cells in hematogenesis which proliferate and differentiate to PBL after irradiation. In in vitro colony formation method AMM demonstrated a protective effect on the survival of GM-CFC, a hematopoietic progenitor cells. Differential action on cancer and normal tissue by AMM and cytochrome C combined with radiotherapy was demonstrated. AMM in combination with cytochrome C augumented natural killer (NK) cells activity in KSN nude mice, protected potent NK cells in patients with lung cancer against radiotherapy and sensitized the human lung cancer xenografts to radiotherapy. Thus, AMM and cytochrome C may have the potential as a differential modulator of radiosensitivity of normal tissues and of tumors.